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Editor’s Choice Articles

Editor’s Choice articles are based on recommendations by the scientific editors of MDPI journals from around the world. Editors select a small number of articles recently published in the journal that they believe will be particularly interesting to readers, or important in the respective research area. The aim is to provide a snapshot of some of the most exciting work published in the various research areas of the journal.

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34 pages, 1983 KiB  
Review
The Neural Correlates of Developmental Prosopagnosia: Twenty-Five Years on
by Valerio Manippa, Annalisa Palmisano, Martina Ventura and Davide Rivolta
Brain Sci. 2023, 13(10), 1399; https://doi.org/10.3390/brainsci13101399 - 30 Sep 2023
Cited by 8 | Viewed by 4752
Abstract
Faces play a crucial role in social interactions. Developmental prosopagnosia (DP) refers to the lifelong difficulty in recognizing faces despite the absence of obvious signs of brain lesions. In recent decades, the neural substrate of this condition has been extensively investigated. While early [...] Read more.
Faces play a crucial role in social interactions. Developmental prosopagnosia (DP) refers to the lifelong difficulty in recognizing faces despite the absence of obvious signs of brain lesions. In recent decades, the neural substrate of this condition has been extensively investigated. While early neuroimaging studies did not reveal significant functional and structural abnormalities in the brains of individuals with developmental prosopagnosia (DPs), recent evidence identifies abnormalities at multiple levels within DPs’ face-processing networks. The current work aims to provide an overview of the convergent and contrasting findings by examining twenty-five years of neuroimaging literature on the anatomo-functional correlates of DP. We included 55 original papers, including 63 studies that compared the brain structure (MRI) and activity (fMRI, EEG, MEG) of healthy control participants and DPs. Despite variations in methods, procedures, outcomes, sample selection, and study design, this scoping review suggests that morphological, functional, and electrophysiological features characterize DPs’ brains, primarily within the ventral visual stream. Particularly, the functional and anatomical connectivity between the Fusiform Face Area and the other face-sensitive regions seems strongly impaired. The cognitive and clinical implications as well as the limitations of these findings are discussed in light of the available knowledge and challenges in the context of DP. Full article
(This article belongs to the Special Issue Insights into Developmental Prosopagnosia)
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23 pages, 1272 KiB  
Review
The Interplay between Mitochondrial Dysfunction and Ferroptosis during Ischemia-Associated Central Nervous System Diseases
by He-Yan Tian, Bo-Yang Huang, Hui-Fang Nie, Xiang-Yu Chen, Yue Zhou, Tong Yang, Shao-Wu Cheng, Zhi-Gang Mei and Jin-Wen Ge
Brain Sci. 2023, 13(10), 1367; https://doi.org/10.3390/brainsci13101367 - 25 Sep 2023
Cited by 15 | Viewed by 3209
Abstract
Cerebral ischemia, a leading cause of disability and mortality worldwide, triggers a cascade of molecular and cellular pathologies linked to several central nervous system (CNS) disorders. These disorders primarily encompass ischemic stroke, Alzheimer’s disease (AD), Parkinson’s disease (PD), epilepsy, and other CNS conditions. [...] Read more.
Cerebral ischemia, a leading cause of disability and mortality worldwide, triggers a cascade of molecular and cellular pathologies linked to several central nervous system (CNS) disorders. These disorders primarily encompass ischemic stroke, Alzheimer’s disease (AD), Parkinson’s disease (PD), epilepsy, and other CNS conditions. Despite substantial progress in understanding and treating the underlying pathological processes in various neurological diseases, there is still a notable absence of effective therapeutic approaches aimed specifically at mitigating the damage caused by these illnesses. Remarkably, ischemia causes severe damage to cells in ischemia-associated CNS diseases. Cerebral ischemia initiates oxygen and glucose deprivation, which subsequently promotes mitochondrial dysfunction, including mitochondrial permeability transition pore (MPTP) opening, mitophagy dysfunction, and excessive mitochondrial fission, triggering various forms of cell death such as autophagy, apoptosis, as well as ferroptosis. Ferroptosis, a novel type of regulated cell death (RCD), is characterized by iron-dependent accumulation of lethal reactive oxygen species (ROS) and lipid peroxidation. Mitochondrial dysfunction and ferroptosis both play critical roles in the pathogenic progression of ischemia-associated CNS diseases. In recent years, growing evidence has indicated that mitochondrial dysfunction interplays with ferroptosis to aggravate cerebral ischemia injury. However, the potential connections between mitochondrial dysfunction and ferroptosis in cerebral ischemia have not yet been clarified. Thus, we analyzed the underlying mechanism between mitochondrial dysfunction and ferroptosis in ischemia-associated CNS diseases. We also discovered that GSH depletion and GPX4 inactivation cause lipoxygenase activation and calcium influx following cerebral ischemia injury, resulting in MPTP opening and mitochondrial dysfunction. Additionally, dysfunction in mitochondrial electron transport and an imbalanced fusion-to-fission ratio can lead to the accumulation of ROS and iron overload, which further contribute to the occurrence of ferroptosis. This creates a vicious cycle that continuously worsens cerebral ischemia injury. In this study, our focus is on exploring the interplay between mitochondrial dysfunction and ferroptosis, which may offer new insights into potential therapeutic approaches for the treatment of ischemia-associated CNS diseases. Full article
(This article belongs to the Special Issue Advances in Cell Therapy of Neurodegenerative Diseases)
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22 pages, 3602 KiB  
Article
Brain Tumor Classification from MRI Using Image Enhancement and Convolutional Neural Network Techniques
by Zahid Rasheed, Yong-Kui Ma, Inam Ullah, Yazeed Yasin Ghadi, Muhammad Zubair Khan, Muhammad Abbas Khan, Akmalbek Abdusalomov, Fayez Alqahtani and Ahmed M. Shehata
Brain Sci. 2023, 13(9), 1320; https://doi.org/10.3390/brainsci13091320 - 14 Sep 2023
Cited by 32 | Viewed by 4256
Abstract
The independent detection and classification of brain malignancies using magnetic resonance imaging (MRI) can present challenges and the potential for error due to the intricate nature and time-consuming process involved. The complexity of the brain tumor identification process primarily stems from the need [...] Read more.
The independent detection and classification of brain malignancies using magnetic resonance imaging (MRI) can present challenges and the potential for error due to the intricate nature and time-consuming process involved. The complexity of the brain tumor identification process primarily stems from the need for a comprehensive evaluation spanning multiple modules. The advancement of deep learning (DL) has facilitated the emergence of automated medical image processing and diagnostics solutions, thereby offering a potential resolution to this issue. Convolutional neural networks (CNNs) represent a prominent methodology in visual learning and image categorization. The present study introduces a novel methodology integrating image enhancement techniques, specifically, Gaussian-blur-based sharpening and Adaptive Histogram Equalization using CLAHE, with the proposed model. This approach aims to effectively classify different categories of brain tumors, including glioma, meningioma, and pituitary tumor, as well as cases without tumors. The algorithm underwent comprehensive testing using benchmarked data from the published literature, and the results were compared with pre-trained models, including VGG16, ResNet50, VGG19, InceptionV3, and MobileNetV2. The experimental findings of the proposed method demonstrated a noteworthy classification accuracy of 97.84%, a precision success rate of 97.85%, a recall rate of 97.85%, and an F1-score of 97.90%. The results presented in this study showcase the exceptional accuracy of the proposed methodology in accurately classifying the most commonly occurring brain tumor types. The technique exhibited commendable generalization properties, rendering it a valuable asset in medicine for aiding physicians in making precise and proficient brain diagnoses. Full article
(This article belongs to the Special Issue Advances of AI in Neuroimaging)
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18 pages, 724 KiB  
Review
Are Sex Differences in Collegiate and High School Sports-Related Concussion Reflected in the Guidelines? A Scoping Review
by Patryk A. Musko and Andreas K. Demetriades
Brain Sci. 2023, 13(9), 1310; https://doi.org/10.3390/brainsci13091310 - 12 Sep 2023
Cited by 9 | Viewed by 2421
Abstract
Background: Sport-related concussion (SRC) is a common sport injury. Females are participating in sports at increasing rates, and there is growing awareness that female athletes may be more vulnerable to SRC. Objectives: We aimed to identify sex differences in epidemiology, clinical [...] Read more.
Background: Sport-related concussion (SRC) is a common sport injury. Females are participating in sports at increasing rates, and there is growing awareness that female athletes may be more vulnerable to SRC. Objectives: We aimed to identify sex differences in epidemiology, clinical manifestation and assessment of SRC and examine how these relate to the 6th International Conference on Concussion in Sport (ICCS). Methods: We conducted a scoping review of the Medline database and identified 58 studies examining the effects of sex on SRC in collegiate and high school athletes that were written in English and published in a peer-reviewed journal between March 2012 and March 2022. Results: We found that female athletes suffer higher rates of concussion in sex-comparable sports, in particular soccer. Female athletes experience more somatic symptoms—headache/migraine/sleep disturbance—and may take longer to recover from concussion. Sex differences were also identified regarding some aspects of sideline concussion assessment with the Sport Concussion Assessment Tool. Conclusions: Females are at greater risk and experience SRC differently than males; this is mostly likely due to a combination of biomechanical factors, differences in neck musculature and hormonal and social factors. Sex differences are not widely addressed by the 6th ICSS, which informs many sports’ concussion protocols. Full article
(This article belongs to the Special Issue New Trends and Technologies in Modern Neurosurgery)
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23 pages, 1937 KiB  
Systematic Review
Photosensitizers for Photodynamic Therapy of Brain Cancers—A Review
by Dorota Bartusik-Aebisher, Paweł Woźnicki, Klaudia Dynarowicz and David Aebisher
Brain Sci. 2023, 13(9), 1299; https://doi.org/10.3390/brainsci13091299 - 8 Sep 2023
Cited by 15 | Viewed by 2975
Abstract
On average, there are about 300,000 new cases of brain cancer each year. Studies have shown that brain and central nervous system tumors are among the top ten causes of death. Due to the extent of this problem and the percentage of patients [...] Read more.
On average, there are about 300,000 new cases of brain cancer each year. Studies have shown that brain and central nervous system tumors are among the top ten causes of death. Due to the extent of this problem and the percentage of patients suffering from brain tumors, innovative therapeutic treatment methods are constantly being sought. One such innovative therapeutic method is photodynamic therapy (PDT). Photodynamic therapy is an alternative and unique technique widely used in dermatology and other fields of medicine for the treatment of oncological and nononcological lesions. Photodynamic therapy consists of the destruction of cancer cells and inducing inflammatory changes by using laser light of a specific wavelength in combination with the application of a photosensitizer. The most commonly used photosensitizers include 5-aminolevulinic acid for the enzymatic generation of protoporphyrin IX, Temoporfin—THPC, Photofrin, Hypericin and Talaporfin. This paper reviews the photosensitizers commonly used in photodynamic therapy for brain tumors. An overview of all three generations of photosensitizers is presented. Along with an indication of the limitations of the treatment of brain tumors, intraoperative photodynamic therapy and its possibilities are described as an alternative therapeutic method. Full article
(This article belongs to the Special Issue Advances in Diagnosis and Treatment of Brain Tumors and Nervous System Tumors)
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13 pages, 601 KiB  
Review
Diagnosis and Management of Seronegative Myasthenia Gravis: Lights and Shadows
by Claudia Vinciguerra, Liliana Bevilacqua, Antonino Lupica, Federica Ginanneschi, Giuseppe Piscosquito, Nicasio Rini, Alessandro Rossi, Paolo Barone, Filippo Brighina and Vincenzo Di Stefano
Brain Sci. 2023, 13(9), 1286; https://doi.org/10.3390/brainsci13091286 - 5 Sep 2023
Cited by 16 | Viewed by 5240
Abstract
Myasthenia gravis (MG) is an antibody-mediated neuromuscular disease affecting the neuromuscular junction. In most cases, autoantibodies can be detected in the sera of MG patients, thus aiding in diagnosis and allowing for early screening. However, there is a small proportion of patients who [...] Read more.
Myasthenia gravis (MG) is an antibody-mediated neuromuscular disease affecting the neuromuscular junction. In most cases, autoantibodies can be detected in the sera of MG patients, thus aiding in diagnosis and allowing for early screening. However, there is a small proportion of patients who have no detectable auto-antibodies, a condition termed “seronegative MG” (SnMG). Several factors contribute to this, including laboratory test inaccuracies, decreased antibody production, immunosuppressive therapy, immunodeficiencies, antigen depletion, and immune-senescence. The diagnosis of SnMG is more challenging and is based on clinical features and neurophysiological tests. The early identification of these patients is needed in order to ensure early treatment and prevent complications. This narrative review aims to examine the latest updates on SnMG, defining the clinical characteristics of affected patients, diagnostic methods, management, and therapeutic scenarios. Full article
(This article belongs to the Special Issue Diagnosis, Therapy and Rehabilitation in Neuromuscular Diseases)
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16 pages, 879 KiB  
Review
Neuroprotective Potential of Flavonoids in Brain Disorders
by Syed Hasan, Nabeel Khatri, Zainab N. Rahman, Amanda A. Menezes, Joud Martini, Faheem Shehjar, Numa Mujeeb and Zahoor A. Shah
Brain Sci. 2023, 13(9), 1258; https://doi.org/10.3390/brainsci13091258 - 29 Aug 2023
Cited by 15 | Viewed by 3812
Abstract
Flavonoids are a large subgroup of polyphenols known to be sourced from over 6000 natural products, including fruits, vegetables, bark, and herbs. Due to their antioxidant properties, flavonoids have been implicated as a therapy source for many diseases and conditions, including inflammation, vasculitis, [...] Read more.
Flavonoids are a large subgroup of polyphenols known to be sourced from over 6000 natural products, including fruits, vegetables, bark, and herbs. Due to their antioxidant properties, flavonoids have been implicated as a therapy source for many diseases and conditions, including inflammation, vasculitis, venous insufficiency, and hemorrhoids. Currently, some flavonoids are being researched for their antioxidant ability concerning neuroprotection. These flavonoids can penetrate the blood–brain barrier and, depending on the specific flavonoid, retain adequate bioavailability in certain brain regions. Further data suggest that flavonoids could have a strong anti-inflammatory effect in the brain, which not only could be a robust therapeutic source for known neuroinflammatory diseases such as Alzheimer’s Disease or Parkinson’s Disease but also could be a therapeutic source for ischemic or hemorrhagic conditions such as a stroke. While flavonoid toxicity exists, they are relatively safe and non-invasive drugs from natural origins. As such, exploring the known mechanisms and therapies may highlight and establish flavonoid therapy as a viable source of therapy for stroke patients. As stated, many flavonoids are already being isolated, purified, and implemented in both in vitro and in vivo experiments. As these flavonoids proceed to clinical trials, it will be important to understand how they function as a therapy, primarily as antioxidants, and by other secondary mechanisms. This review aims to elucidate those mechanisms and explore the neuroprotective role of flavonoids. Full article
(This article belongs to the Special Issue Cellular and Molecular Basis of Neurodegenerative Disease)
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29 pages, 2324 KiB  
Systematic Review
The Role of Serotonin in Fear Learning and Memory: A Systematic Review of Human Studies
by Francesco Tortora, Abed L. Hadipour, Simone Battaglia, Alessandra Falzone, Alessio Avenanti and Carmelo M. Vicario
Brain Sci. 2023, 13(8), 1197; https://doi.org/10.3390/brainsci13081197 - 12 Aug 2023
Cited by 26 | Viewed by 6461
Abstract
Fear is characterized by distinct behavioral and physiological responses that are essential for the survival of the human species. Fear conditioning (FC) serves as a valuable model for studying the acquisition, extinction, and expression of fear. The serotonin (5-hydroxytryptamine, 5-HT) system is known [...] Read more.
Fear is characterized by distinct behavioral and physiological responses that are essential for the survival of the human species. Fear conditioning (FC) serves as a valuable model for studying the acquisition, extinction, and expression of fear. The serotonin (5-hydroxytryptamine, 5-HT) system is known to play a significant role in emotional and motivational aspects of human behavior, including fear learning and expression. Accumulating evidence from both animal and human studies suggests that brain regions involved in FC, such as the amygdala, hippocampus, and prefrontal cortex, possess a high density of 5-HT receptors, implicating the crucial involvement of serotonin in aversive learning. Additionally, studies exploring serotonin gene polymorphisms have indicated their potential influence on FC. Therefore, the objective of this work was to review the existing evidence linking 5-HT with fear learning and memory in humans. Through a comprehensive screening of the PubMed and Web of Science databases, 29 relevant studies were included in the final review. These studies investigated the relationship between serotonin and fear learning using drug manipulations or by studying 5-HT-related gene polymorphisms. The results suggest that elevated levels of 5-HT enhance aversive learning, indicating that the modulation of serotonin 5-HT2A receptors regulates the expression of fear responses in humans. Understanding the role of this neurochemical messenger in associative aversive learning can provide insights into psychiatric disorders such as anxiety and post-traumatic stress disorder (PTSD), among others. Full article
(This article belongs to the Special Issue Linkage among Cognition, Emotion and Behavior)
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23 pages, 375 KiB  
Review
Novel Compounds in the Treatment of Schizophrenia—A Selective Review
by Evangelia Maria Tsapakis, Kalliopi Diakaki, Apostolos Miliaras and Konstantinos N. Fountoulakis
Brain Sci. 2023, 13(8), 1193; https://doi.org/10.3390/brainsci13081193 - 11 Aug 2023
Cited by 12 | Viewed by 6359
Abstract
Schizophrenia is a chronic neuropsychiatric syndrome that significantly impacts daily function and quality of life. All of the available guidelines suggest a combined treatment approach with pharmacologic agents and psychological interventions. However, one in three patients is a non-responder, the effect on negative [...] Read more.
Schizophrenia is a chronic neuropsychiatric syndrome that significantly impacts daily function and quality of life. All of the available guidelines suggest a combined treatment approach with pharmacologic agents and psychological interventions. However, one in three patients is a non-responder, the effect on negative and cognitive symptoms is limited, and many drug-related adverse effects complicate clinical management. As a result, discovering novel drugs for schizophrenia presents a significant challenge for psychopharmacology. This selective review of the literature aims to outline the current knowledge on the aetiopathogenesis of schizophrenia and to present the recently approved and newly discovered pharmacological substances in treating schizophrenia. We discuss ten novel drugs, three of which have been approved by the FDA (Olanzapine/Samidorphan, Lumateperone, and Pimavanserin). The rest are under clinical trial investigation (Brilaroxazine, Xanomeline/Trospium, Emraclidine, Ulotaront, Sodium Benzoate, Luvadaxistat, and Iclepertin). However, additional basic and clinical research is required not only to improve our understanding of the neurobiology and the potential novel targets in the treatment of schizophrenia, but also to establish more effective therapeutical interventions for the syndrome, including the attenuation of negative and cognitive symptoms and avoiding dopamine blockade-related adverse effects. Full article
(This article belongs to the Special Issue New Insights in Psychiatric Disorder Psychopharmacology)
23 pages, 1247 KiB  
Review
Visual Dysfunction in Parkinson’s Disease
by Francisco Nieto-Escamez, Esteban Obrero-Gaitán and Irene Cortés-Pérez
Brain Sci. 2023, 13(8), 1173; https://doi.org/10.3390/brainsci13081173 - 7 Aug 2023
Cited by 15 | Viewed by 3400
Abstract
Non-motor symptoms in Parkinson’s disease (PD) include ocular, visuoperceptive, and visuospatial impairments, which can occur as a result of the underlying neurodegenerative process. Ocular impairments can affect various aspects of vision and eye movement. Thus, patients can show dry eyes, blepharospasm, reduced blink [...] Read more.
Non-motor symptoms in Parkinson’s disease (PD) include ocular, visuoperceptive, and visuospatial impairments, which can occur as a result of the underlying neurodegenerative process. Ocular impairments can affect various aspects of vision and eye movement. Thus, patients can show dry eyes, blepharospasm, reduced blink rate, saccadic eye movement abnormalities, smooth pursuit deficits, and impaired voluntary and reflexive eye movements. Furthermore, visuoperceptive impairments affect the ability to perceive and recognize visual stimuli accurately, including impaired contrast sensitivity and reduced visual acuity, color discrimination, and object recognition. Visuospatial impairments are also remarkable, including difficulties perceiving and interpreting spatial relationships between objects and difficulties judging distances or navigating through the environment. Moreover, PD patients can present visuospatial attention problems, with difficulties attending to visual stimuli in a spatially organized manner. Moreover, PD patients also show perceptual disturbances affecting their ability to interpret and determine meaning from visual stimuli. And, for instance, visual hallucinations are common in PD patients. Nevertheless, the neurobiological bases of visual-related disorders in PD are complex and not fully understood. This review intends to provide a comprehensive description of visual disturbances in PD, from sensory to perceptual alterations, addressing their neuroanatomical, functional, and neurochemical correlates. Structural changes, particularly in posterior cortical regions, are described, as well as functional alterations, both in cortical and subcortical regions, which are shown in relation to specific neuropsychological results. Similarly, although the involvement of different neurotransmitter systems is controversial, data about neurochemical alterations related to visual impairments are presented, especially dopaminergic, cholinergic, and serotoninergic systems. Full article
(This article belongs to the Special Issue Non-motor Disorders in Parkinson Disease: Basic Science and Advances in Treatment)
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21 pages, 4745 KiB  
Review
Artificial Intelligence Frameworks to Detect and Investigate the Pathophysiology of Spaceflight Associated Neuro-Ocular Syndrome (SANS)
by Joshua Ong, Ethan Waisberg, Mouayad Masalkhi, Sharif Amit Kamran, Kemper Lowry, Prithul Sarker, Nasif Zaman, Phani Paladugu, Alireza Tavakkoli and Andrew G. Lee
Brain Sci. 2023, 13(8), 1148; https://doi.org/10.3390/brainsci13081148 - 30 Jul 2023
Cited by 23 | Viewed by 5370
Abstract
Spaceflight associated neuro-ocular syndrome (SANS) is a unique phenomenon that has been observed in astronauts who have undergone long-duration spaceflight (LDSF). The syndrome is characterized by distinct imaging and clinical findings including optic disc edema, hyperopic refractive shift, posterior globe flattening, and choroidal [...] Read more.
Spaceflight associated neuro-ocular syndrome (SANS) is a unique phenomenon that has been observed in astronauts who have undergone long-duration spaceflight (LDSF). The syndrome is characterized by distinct imaging and clinical findings including optic disc edema, hyperopic refractive shift, posterior globe flattening, and choroidal folds. SANS serves a large barrier to planetary spaceflight such as a mission to Mars and has been noted by the National Aeronautics and Space Administration (NASA) as a high risk based on its likelihood to occur and its severity to human health and mission performance. While it is a large barrier to future spaceflight, the underlying etiology of SANS is not well understood. Current ophthalmic imaging onboard the International Space Station (ISS) has provided further insights into SANS. However, the spaceflight environment presents with unique challenges and limitations to further understand this microgravity-induced phenomenon. The advent of artificial intelligence (AI) has revolutionized the field of imaging in ophthalmology, particularly in detection and monitoring. In this manuscript, we describe the current hypothesized pathophysiology of SANS and the medical diagnostic limitations during spaceflight to further understand its pathogenesis. We then introduce and describe various AI frameworks that can be applied to ophthalmic imaging onboard the ISS to further understand SANS including supervised/unsupervised learning, generative adversarial networks, and transfer learning. We conclude by describing current research in this area to further understand SANS with the goal of enabling deeper insights into SANS and safer spaceflight for future missions. Full article
(This article belongs to the Special Issue Recent Advances in Neuro-Opthalmology)
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13 pages, 284 KiB  
Review
Early Brain Injury and Neuroprotective Treatment after Aneurysmal Subarachnoid Hemorrhage: A Literature Review
by Xiaopeng Li, Lang Zeng, Xuanzhen Lu, Kun Chen, Maling Yu, Baofeng Wang and Min Zhao
Brain Sci. 2023, 13(7), 1083; https://doi.org/10.3390/brainsci13071083 - 17 Jul 2023
Cited by 12 | Viewed by 2297
Abstract
Early brain injury (EBI) subsequent to subarachnoid hemorrhage (SAH) is strongly associated with delayed cerebral ischemia and poor patient prognosis. Based on investigations into the molecular mechanisms underlying EBI, neurovascular dysfunction resulting from SAH can be attributed to a range of pathological processes, [...] Read more.
Early brain injury (EBI) subsequent to subarachnoid hemorrhage (SAH) is strongly associated with delayed cerebral ischemia and poor patient prognosis. Based on investigations into the molecular mechanisms underlying EBI, neurovascular dysfunction resulting from SAH can be attributed to a range of pathological processes, such as microvascular alterations in brain tissue, ionic imbalances, blood–brain barrier disruption, immune–inflammatory responses, oxidative stress, and activation of cell death pathways. Research progress presents a variety of promising therapeutic approaches for the preservation of neurological function following SAH, including calcium channel antagonists, endothelin-1 receptor blockers, antiplatelet agents, anti-inflammatory agents, and anti-oxidative stress agents. EBI can be mitigated following SAH through neuroprotective measures. To enhance our comprehension of the relevant molecular pathways involved in brain injury, including brain ischemia–hypoxic injury, neuroimmune inflammation activation, and the activation of various cell-signaling pathways, following SAH, it is essential to investigate the evolution of these multifaceted pathophysiological processes. Facilitating neural repair following a brain injury is critical for improving patient survival rates and quality of life. Full article
(This article belongs to the Special Issue Ischemic Brain Injury: Cerebral Metabolism and Imaging)
13 pages, 694 KiB  
Review
Regulatory Clearance and Approval of Therapeutic Protocols of Transcranial Magnetic Stimulation for Psychiatric Disorders
by Gonçalo Cotovio, Fabiana Ventura, Daniel Rodrigues da Silva, Patrícia Pereira and Albino J. Oliveira-Maia
Brain Sci. 2023, 13(7), 1029; https://doi.org/10.3390/brainsci13071029 - 5 Jul 2023
Cited by 12 | Viewed by 4006
Abstract
Non-invasive brain stimulation techniques (NIBS) have been widely used in both clinical and research contexts in neuropsychiatry. They are safe and well-tolerated, making NIBS an interesting option for application in different settings. Transcranial magnetic stimulation (TMS) is one of these strategies. It uses [...] Read more.
Non-invasive brain stimulation techniques (NIBS) have been widely used in both clinical and research contexts in neuropsychiatry. They are safe and well-tolerated, making NIBS an interesting option for application in different settings. Transcranial magnetic stimulation (TMS) is one of these strategies. It uses electromagnetic pulses for focal modulate ion of neuronal activity in brain cortical regions. When pulses are applied repeatedly (repetitive transcranial magnetic stimulation—rTMS), they are thought to induce long-lasting neuroplastic effects, proposed to be a therapeutic mechanism for rTMS, with efficacy and safety initially demonstrated for treatment-resistant depression (TRD). Since then, many rTMS treatment protocols emerged for other difficult to treat psychiatric conditions. Moreover, multiple clinical studies, including large multi-center trials and several meta-analyses, have confirmed its clinical efficacy in different neuropsychiatric disorders, resulting in evidence-based guidelines and recommendations. Currently, rTMS is cleared by multiple regulatory agencies for the treatment of TRD, depression with comorbid anxiety disorders, obsessive compulsive disorder, and substance use disorders, such as smoking cessation. Importantly, current research supports the potential future use of rTMS for other psychiatric syndromes, including the negative symptoms of schizophrenia and post-traumatic stress disorder. More precise knowledge of formal indications for rTMS therapeutic use in psychiatry is critical to enhance clinical decision making in this area. Full article
(This article belongs to the Special Issue Biomarkers to Guide Non-invasive Brain Stimulation in Psychiatric Disorders)
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8 pages, 251 KiB  
Review
Animal Models of Ischemic Stroke with Different Forms of Middle Cerebral Artery Occlusion
by Lang Zeng, Shengqi Hu, Lingcheng Zeng, Rudong Chen, Hua Li, Jiasheng Yu and Hongkuan Yang
Brain Sci. 2023, 13(7), 1007; https://doi.org/10.3390/brainsci13071007 - 29 Jun 2023
Cited by 13 | Viewed by 4496
Abstract
Ischemic stroke is a common type of stroke that significantly affects human well-being and quality of life. In order to further characterize the pathophysiology of ischemic stroke and develop new treatment strategies, ischemic stroke models with controllable and consistent response to potential clinical [...] Read more.
Ischemic stroke is a common type of stroke that significantly affects human well-being and quality of life. In order to further characterize the pathophysiology of ischemic stroke and develop new treatment strategies, ischemic stroke models with controllable and consistent response to potential clinical treatments are urgently needed. The middle cerebral artery occlusion (MCAO) model is currently the most widely used animal model of ischemic stroke. This review discusses various methods for constructing the MCAO model and compares their advantages and disadvantages in order to provide better approaches for studying ischemic stroke. Full article
(This article belongs to the Special Issue Ischemic Brain Injury: Cerebral Metabolism and Imaging)
17 pages, 1466 KiB  
Systematic Review
Toxicity of Synthetic Cannabinoids in K2/Spice: A Systematic Review
by Mariana Campello de Oliveira, Mariana Capelo Vides, Dângela Layne Silva Lassi, Julio Torales, Antonio Ventriglio, Henrique Silva Bombana, Vilma Leyton, Cintia de Azevedo-Marques Périco, André Brooking Negrão, André Malbergier and João Maurício Castaldelli-Maia
Brain Sci. 2023, 13(7), 990; https://doi.org/10.3390/brainsci13070990 - 24 Jun 2023
Cited by 17 | Viewed by 10136
Abstract
(1) Background: Synthetic cannabinoids (SCs) are emerging drugs of abuse sold as ‘K2’, ‘K9’ or ‘Spice’. Evidence shows that using SCs products leads to greater health risks than cannabis. They have been associated with greater toxicity and higher addiction potential unrelated to the [...] Read more.
(1) Background: Synthetic cannabinoids (SCs) are emerging drugs of abuse sold as ‘K2’, ‘K9’ or ‘Spice’. Evidence shows that using SCs products leads to greater health risks than cannabis. They have been associated with greater toxicity and higher addiction potential unrelated to the primary psychoactive component of marijuana, Δ9-tetrahydrocannabinol (Δ9-THC). Moreover, early cases of intoxication and death related to SCs highlight the inherent danger that may accompany the use of these substances. However, there is limited knowledge of the toxicology of Spice ingredients. This systematic review intends to analyze the toxicity of SCs compounds in Spice/K2 drugs. (2) Methods: Studies analyzing synthetic cannabinoid toxicity and dependence were included in the present review. We searched the PubMed database of the US National Library of Medicine, Google Scholar, CompTox Chemicals, and Web of Science up to May 2022. (3) Results: Sixty-four articles reporting the effects of synthetic cannabinoids in humans were included in our review. Ten original papers and fifty-four case studies were also included. Fourteen studies reported death associated with synthetic cannabinoid use, with AB-CHMINACA and MDMB-CHMICA being the main reported SCs. Tachycardia and seizures were the most common toxicity symptoms. The prevalence of neuropsychiatric symptoms was higher in third-generation SCs. (4) Conclusion: SCs may exhibit higher toxicity than THC and longer-lasting effects. Their use may be harmful, especially in people with epilepsy and schizophrenia, because of the increased risk of the precipitation of psychiatric and neurologic disorders. Compared to other drugs, SCs have a higher potential to trigger a convulsive crisis, a decline in consciousness, and hemodynamic changes. Therefore, it is crucial to clarify their potential harms and increase the availability of toxicology data in both clinical and research settings. Full article
(This article belongs to the Special Issue Substance Abuse and Mental Health)
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14 pages, 702 KiB  
Review
Is It Time for a Paradigm Shift in the Treatment of Schizophrenia? The Use of Inflammation-Reducing and Neuroprotective Drugs—A Review
by Antonino Messina, Carmen Concerto, Alessandro Rodolico, Antonino Petralia, Filippo Caraci and Maria Salvina Signorelli
Brain Sci. 2023, 13(6), 957; https://doi.org/10.3390/brainsci13060957 - 15 Jun 2023
Cited by 20 | Viewed by 4021
Abstract
Comprehending the pathogenesis of schizophrenia represents a challenge for global mental health. To date, although it is evident that alterations in dopaminergic, serotonergic, and glutamatergic neurotransmission underlie the clinical expressiveness of the disease, neuronal disconnections represent only an epiphenomenon. In recent years, several [...] Read more.
Comprehending the pathogenesis of schizophrenia represents a challenge for global mental health. To date, although it is evident that alterations in dopaminergic, serotonergic, and glutamatergic neurotransmission underlie the clinical expressiveness of the disease, neuronal disconnections represent only an epiphenomenon. In recent years, several clinical studies have converged on the hypothesis of microglia hyperactivation and a consequent neuroinflammatory state as a pathogenic substrate of schizophrenia. Prenatal, perinatal, and postnatal factors can cause microglia to switch from M2 anti-inflammatory to M1 pro-inflammatory states. A continuous mild neuroinflammatory state progressively leads to neuronal loss, a reduction in dendritic spines, and myelin degeneration. The augmentation of drugs that reduce neuroinflammation to antipsychotics could be an effective therapeutic modality in managing schizophrenia. This review will consider studies in which drugs with anti-inflammatory and neuroprotective properties have been used in addition to antipsychotic treatment in patients with schizophrenia. Full article
(This article belongs to the Special Issue New Insights in Psychiatric Disorder Psychopharmacology)
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10 pages, 16129 KiB  
Article
Do Individuals with Spinal Cord Injury Benefit from Semi-Immersive Virtual Reality Cognitive Training? Preliminary Results from an Exploratory Study on an Underestimated Problem
by Maria Grazia Maggio, Mirjam Bonanno, Alfredo Manuli, Maria Pia Onesta, Rosaria De Luca, Angelo Quartarone and Rocco Salvatore Calabrò
Brain Sci. 2023, 13(6), 945; https://doi.org/10.3390/brainsci13060945 - 13 Jun 2023
Cited by 8 | Viewed by 2113
Abstract
A spinal cord injury (SCI) is damage to any part of the spinal cord, caused by traumatic or non-traumatic events. Clinically, SCI is associated with partial or complete loss of motor, sensory, and autonomic functions below the site of injury. However, cognitive alterations [...] Read more.
A spinal cord injury (SCI) is damage to any part of the spinal cord, caused by traumatic or non-traumatic events. Clinically, SCI is associated with partial or complete loss of motor, sensory, and autonomic functions below the site of injury. However, cognitive alterations in specific domains can also occur. The aim of this study was to evaluate the effects of semi-immersive virtual reality (VR) cognitive training (using the BTS Nirvana, Italy) in promoting global functional recovery in patients with SCI. Forty-two SCI patients were included in this retrospective case-control study, and the analysis was carried out using an electronic data retrieval system. The enrolled patients were divided into two groups with the same demographic and medical characteristics: the control group (CG: 21 patients) participated in traditional therapy, whereas the experimental group (EG: 21 patients) received training using semi-immersive VR. In both groups, there were patients with A- or B-grade impairments according to the American Spinal Injury Association (ASIA) scale. Both study groups underwent the same amount of cognitive training (but using a different type of training: conventional vs. innovative), consisting of three weekly sessions for eight weeks (24 sessions in total), each session lasting approximately sixty minutes, as well as the same amount of physiotherapy. The effect of the two treatments (EG/CG) was significantly different in global cognitive functioning (MOCA: p = 0.001), mood (BDI: p = 0.006), and overall quality of life (SF12 Total: p < 0.001), especially in physical perception (SF12-Physics: p = 0.004). Our results suggest that SCI patients could benefit from cognitive training using semi-immersive VR. Indeed, the integration of cognitive exercises that require movement and provide increased feedback could allow for better motor and cognitive recovery in people with SCI. Full article
(This article belongs to the Section Neurorehabilitation)
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13 pages, 611 KiB  
Article
Association of Motoric Cognitive Risk Syndrome with Sarcopenia and Systemic Inflammation in Pre-Frail Older Adults
by Reshma Aziz Merchant, Yiong Huak Chan, Denishkrshna Anbarasan and Ivan Aprahamian
Brain Sci. 2023, 13(6), 936; https://doi.org/10.3390/brainsci13060936 - 9 Jun 2023
Cited by 9 | Viewed by 2912
Abstract
Motoric cognitive risk syndrome (MCR) is defined by the presence of slow gait and subjective cognitive decline. It is well recognized as a prodrome for dementia, but the biological mechanism and trajectory for MCR are still lacking. The objective of this study was [...] Read more.
Motoric cognitive risk syndrome (MCR) is defined by the presence of slow gait and subjective cognitive decline. It is well recognized as a prodrome for dementia, but the biological mechanism and trajectory for MCR are still lacking. The objective of this study was to explore the association of MCR with body composition, including sarcopenia and systemic inflammation, in pre-frail older adults in a cross-sectional study of 397 pre-frail community-dwelling older adults. Data on demographics, physical function, frailty, cognition (Montreal Cognitive Assessment (MoCA)), perceived health and depression were collected. Body composition was measured using a bioelectrical impedance analyzer. Systemic inflammatory biomarkers, such as progranulin, growth differentiation factor-15 (GDF-15), interleukin-10 (IL-10), interleukin-6 and tumor necrosis factor-α (TNF-α), were collected. Univariate and multivariate logistic regression were used to analyze the association between MCR, body composition, sarcopenia and systemic inflammatory biomarkers. The prevalence of MCR was 14.9%. They were significantly older and there were more females, depression, functional impairment, lower education, physical activity and MoCA scores. Body fat percentage (BF%), fat mass index, fat to fat free mass ratio (FM/FFM) and sarcopenia prevalence were significantly higher in MCR. Serum GDF-15 and TNF-α levels were highest with progranulin/TNF-α and IL-10/TNF-α ratio lowest in MCR. Compared to healthy patients, MCR was significantly associated with sarcopenia (aOR 2.62; 95% CI 1.46–3.17), BF% (aOR 1.06; 95% CI 1.01–1.12), FMI (aOR 1.16; 95% CI 1.02–1.30) and FM/FFM (aOR 6.38; 95% CI 1.20–33.98). The association of IL-10 to TNF-α ratio (aOR 0.98, 95% CI 0.97–0.99) and IL-10 (aOR 2.22, 95% CI 0.05–0.98) with MCR were independent of sarcopenia and BF%. Longitudinal population studies are needed to understand the role of body fat indices and IL-10 in pre-frail older adults with MCR and trajectory to dementia. Full article
(This article belongs to the Special Issue Advances in Research on Brain Health and Dementia: Prevention and Early Detection of Cognitive Decline and Dementia)
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22 pages, 787 KiB  
Review
Distribution of Iron, Copper, Zinc and Cadmium in Glia, Their Influence on Glial Cells and Relationship with Neurodegenerative Diseases
by Aleksandra Górska, Agnieszka Markiewicz-Gospodarek, Renata Markiewicz, Zuzanna Chilimoniuk, Bartosz Borowski, Mateusz Trubalski and Katarzyna Czarnek
Brain Sci. 2023, 13(6), 911; https://doi.org/10.3390/brainsci13060911 - 5 Jun 2023
Cited by 14 | Viewed by 3501
Abstract
Recent data on the distribution and influence of copper, zinc and cadmium in glial cells are summarized. This review also examines the relationship between those metals and their role in neurodegenerative diseases like Alzheimer disease, multiple sclerosis, Parkinson disease and Amyotrophic lateral sclerosis, [...] Read more.
Recent data on the distribution and influence of copper, zinc and cadmium in glial cells are summarized. This review also examines the relationship between those metals and their role in neurodegenerative diseases like Alzheimer disease, multiple sclerosis, Parkinson disease and Amyotrophic lateral sclerosis, which have become a great challenge for today’s physicians. The studies suggest that among glial cells, iron has the highest concentration in oligodendrocytes, copper in astrocytes and zinc in the glia of hippocampus and cortex. Previous studies have shown neurotoxic effects of copper, iron and manganese, while zinc can have a bidirectional effect, i.e., neurotoxic but also neuroprotective effects depending on the dose and disease state. Recent data point to the association of metals with neurodegeneration through their role in the modulation of protein aggregation. Metals can accumulate in the brain with aging and may be associated with age-related diseases. Full article
(This article belongs to the Section Neuroglia)
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21 pages, 796 KiB  
Systematic Review
The Role of Ketamine in the Treatment of Bipolar Depression: A Scoping Review
by Muhammad Youshay Jawad, Saleha Qasim, Menglu Ni, Ziji Guo, Joshua D. Di Vincenzo, Giacomo d’Andrea, Aniqa Tabassum, Andrea Mckenzie, Sebastian Badulescu, Iria Grande and Roger S. McIntyre
Brain Sci. 2023, 13(6), 909; https://doi.org/10.3390/brainsci13060909 - 4 Jun 2023
Cited by 11 | Viewed by 6156
Abstract
Bipolar depression remains a clinical challenge with a quarter of patients failing to respond to initial conventional treatments. Although ketamine has been extensively studied in unipolar depression, its role in bipolar disorder remains inconclusive. The aim of our scoping review was to comprehensively [...] Read more.
Bipolar depression remains a clinical challenge with a quarter of patients failing to respond to initial conventional treatments. Although ketamine has been extensively studied in unipolar depression, its role in bipolar disorder remains inconclusive. The aim of our scoping review was to comprehensively synthesize the current clinical literature around ketamine use in bipolar depression. A total of 10 clinical studies (5 randomized controlled trials and 5 open label studies) were selected. The preliminary evidence, albeit weak, suggests that ketamine is a promising treatment and calls for further interest from the research community. Overall, ketamine treatment appeared to be tolerable with minimal risk for manic/hypomanic switching and showed some effectiveness across parameters of depression and suicidality. Moreover, ketamine is a potential treatment agent in patients with treatment-resistant bipolar depression with promising data extracted from extant controlled trials and real-world effectiveness studies. Future studies are needed to identify ketamine’s role in acute and maintenance treatment phases of bipolar depression. Moreover, future researchers should study the recurrence prevention and anti-suicidal effects of ketamine in the treatment of bipolar depression. Full article
(This article belongs to the Special Issue Bipolar Disorders: Progressing from Bench to Bedside)
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11 pages, 3580 KiB  
Article
The Use of 3D Printed Models for Surgical Simulation of Cranioplasty in Craniosynostosis as Training and Education
by Jean Francois Uhl, Albert Sufianov, Camillo Ruiz, Yuri Iakimov, Huerta Jose Mogorron, Manuel Encarnacion Ramirez, Guillermo Prat, Barbara Lorea, Matias Baldoncini, Evgeniy Goncharov, Issael Ramirez, José Rafael Cerda Céspedes, Renat Nurmukhametov and Nicola Montemurro
Brain Sci. 2023, 13(6), 894; https://doi.org/10.3390/brainsci13060894 - 1 Jun 2023
Cited by 22 | Viewed by 1667
Abstract
Background: The advance in imaging techniques is useful for 3D models and printing leading to a real revolution in many surgical specialties, in particular, neurosurgery. Methods: We report on a clinical study on the use of 3D printed models to perform cranioplasty in [...] Read more.
Background: The advance in imaging techniques is useful for 3D models and printing leading to a real revolution in many surgical specialties, in particular, neurosurgery. Methods: We report on a clinical study on the use of 3D printed models to perform cranioplasty in patients with craniosynostosis. The participants were recruited from various medical institutions and were divided into two groups: Group A (n = 5) received traditional surgical education (including cadaveric specimens) but without using 3D printed models, while Group B (n = 5) received training using 3D printed models. Results: Group B surgeons had the opportunity to plan different techniques and to simulate the cranioplasty. Group B surgeons reported that models provided a realistic and controlled environment for practicing surgical techniques, allowed for repetitive practice, and helped in visualizing the anatomy and pathology of craniosynostosis. Conclusion: 3D printed models can provide a realistic and controlled environment for neurosurgeons to develop their surgical skills in a safe and efficient manner. The ability to practice on 3D printed models before performing the actual surgery on patients may potentially improve the surgeons’ confidence and competence in performing complex craniosynostosis surgeries. Full article
(This article belongs to the Special Issue Scientific and Clinical Advances in Neurological Surgery)
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17 pages, 672 KiB  
Review
Comorbidity and Overlaps between Autism Spectrum and Borderline Personality Disorder: State of the Art
by Liliana Dell’Osso, Ivan Mirko Cremone, Benedetta Nardi, Valeria Tognini, Lucrezia Castellani, Paola Perrone, Giulia Amatori and Barbara Carpita
Brain Sci. 2023, 13(6), 862; https://doi.org/10.3390/brainsci13060862 - 26 May 2023
Cited by 12 | Viewed by 14940
Abstract
Despite the relationship between Autism spectrum disorder (ASD) and personality disorders (PD) still being scarcely understood, recent investigations increased awareness about significant overlaps between some PD and autism spectrum conditions. In this framework, several studies suggested the presence of similarities between BPD and [...] Read more.
Despite the relationship between Autism spectrum disorder (ASD) and personality disorders (PD) still being scarcely understood, recent investigations increased awareness about significant overlaps between some PD and autism spectrum conditions. In this framework, several studies suggested the presence of similarities between BPD and ASD symptoms and traits, based on the recent literature that increasingly reported increased comorbidity rates and significant symptomatologic overlaps between the two conditions. The aim of this review is to describe the available studies about the prevalence of the association between different forms of autism spectrum (full-fledged clinical conditions as well as subthreshold autistic traits) and BPD. Despite some controversial results and lack of homogeneity in the methods used for the diagnostic assessment, the reviewed literature highlighted how subjects with BPD reported higher scores on tests evaluating the presence of AT compared to a non-clinical population and hypothesized the presence of unrecognized ASD in some BPD patients or vice versa, while also describing a shared vulnerability towards traumatic events, and a greater risk of suicidality in BPD subjects with high autistic traits. However, the specific measure and nature of this association remain to be explored in more depth. Full article
(This article belongs to the Section Psychiatric Diseases)
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10 pages, 793 KiB  
Article
Machine Learning for Early Diagnosis of ATTRv Amyloidosis in Non-Endemic Areas: A Multicenter Study from Italy
by Vincenzo Di Stefano, Francesco Prinzi, Marco Luigetti, Massimo Russo, Stefano Tozza, Paolo Alonge, Angela Romano, Maria Ausilia Sciarrone, Francesca Vitali, Anna Mazzeo, Luca Gentile, Giovanni Palumbo, Fiore Manganelli, Salvatore Vitabile and Filippo Brighina
Brain Sci. 2023, 13(5), 805; https://doi.org/10.3390/brainsci13050805 - 16 May 2023
Cited by 12 | Viewed by 3425
Abstract
Background: Hereditary transthyretin amyloidosis with polyneuropathy (ATTRv) is an adult-onset multisystemic disease, affecting the peripheral nerves, heart, gastrointestinal tract, eyes, and kidneys. Nowadays, several treatment options are available; thus, avoiding misdiagnosis is crucial to starting therapy in early disease stages. However, clinical diagnosis [...] Read more.
Background: Hereditary transthyretin amyloidosis with polyneuropathy (ATTRv) is an adult-onset multisystemic disease, affecting the peripheral nerves, heart, gastrointestinal tract, eyes, and kidneys. Nowadays, several treatment options are available; thus, avoiding misdiagnosis is crucial to starting therapy in early disease stages. However, clinical diagnosis may be difficult, as the disease may present with unspecific symptoms and signs. We hypothesize that the diagnostic process may benefit from the use of machine learning (ML). Methods: 397 patients referring to neuromuscular clinics in 4 centers from the south of Italy with neuropathy and at least 1 more red flag, as well as undergoing genetic testing for ATTRv, were considered. Then, only probands were considered for analysis. Hence, a cohort of 184 patients, 93 with positive and 91 (age- and sex-matched) with negative genetics, was considered for the classification task. The XGBoost (XGB) algorithm was trained to classify positive and negative TTR mutation patients. The SHAP method was used as an explainable artificial intelligence algorithm to interpret the model findings. Results: diabetes, gender, unexplained weight loss, cardiomyopathy, bilateral carpal tunnel syndrome (CTS), ocular symptoms, autonomic symptoms, ataxia, renal dysfunction, lumbar canal stenosis, and history of autoimmunity were used for the model training. The XGB model showed an accuracy of 0.707 ± 0.101, a sensitivity of 0.712 ± 0.147, a specificity of 0.704 ± 0.150, and an AUC-ROC of 0.752 ± 0.107. Using the SHAP explanation, it was confirmed that unexplained weight loss, gastrointestinal symptoms, and cardiomyopathy showed a significant association with the genetic diagnosis of ATTRv, while bilateral CTS, diabetes, autoimmunity, and ocular and renal involvement were associated with a negative genetic test. Conclusions: Our data show that ML might potentially be a useful instrument to identify patients with neuropathy that should undergo genetic testing for ATTRv. Unexplained weight loss and cardiomyopathy are relevant red flags in ATTRv in the south of Italy. Further studies are needed to confirm these findings. Full article
(This article belongs to the Special Issue Attention to Neuromuscular Diseases)
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36 pages, 1617 KiB  
Review
Erectile Dysfunction: Treatments, Advances and New Therapeutic Strategies
by Antonio Argiolas, Francesco Mario Argiolas, Giacomo Argiolas and Maria Rosaria Melis
Brain Sci. 2023, 13(5), 802; https://doi.org/10.3390/brainsci13050802 - 15 May 2023
Cited by 16 | Viewed by 9585
Abstract
Erectile dysfunction (ED) is the inability to get and maintain an adequate penile erection for satisfactory sexual intercourse. Due to its negative impacts on men’s life quality and increase during aging (40% of men between 40 and 70 years), ED has always attracted [...] Read more.
Erectile dysfunction (ED) is the inability to get and maintain an adequate penile erection for satisfactory sexual intercourse. Due to its negative impacts on men’s life quality and increase during aging (40% of men between 40 and 70 years), ED has always attracted researchers of different disciplines, from urology, andrology and neuropharmacology to regenerative medicine, and vascular and prosthesis implant surgery. Locally and/or centrally acting drugs are used to treat ED, e.g., phosphodiesterase 5 inhibitors (first in the list) given orally, and phentolamine, prostaglandin E1 and papaverine injected intracavernously. Preclinical data also show that dopamine D4 receptor agonists, oxytocin and α-MSH analogues may have a role in ED treatment. However, since pro-erectile drugs are given on demand and are not always efficacious, new strategies are being tested for long lasting cures of ED. These include regenerative therapies, e.g., stem cells, plasma-enriched platelets and extracorporeal shock wave treatments to cure damaged erectile tissues. Although fascinating, these therapies are laborious, expensive and not easily reproducible. This leaves old vacuum erection devices and penile prostheses as the only way to get an artificial erection and sexual intercourse with intractable ED, with penile prosthesis used only by accurately selected patients. Full article
(This article belongs to the Section Behavioral Neuroscience)
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14 pages, 4838 KiB  
Article
Trimethylamine N-Oxide Exacerbates Neuroinflammation and Motor Dysfunction in an Acute MPTP Mice Model of Parkinson’s Disease
by Wei Quan, Chen-Meng Qiao, Gu-Yu Niu, Jian Wu, Li-Ping Zhao, Chun Cui, Wei-Jiang Zhao and Yan-Qin Shen
Brain Sci. 2023, 13(5), 790; https://doi.org/10.3390/brainsci13050790 - 12 May 2023
Cited by 12 | Viewed by 2752
Abstract
Observational studies have shown abnormal changes in trimethylamine N-oxide (TMAO) levels in the peripheral circulatory system of Parkinson’s disease (PD) patients. TMAO is a gut microbiota metabolite that can cross the blood–brain barrier and is strongly related to neuroinflammation. Neuroinflammation is one of [...] Read more.
Observational studies have shown abnormal changes in trimethylamine N-oxide (TMAO) levels in the peripheral circulatory system of Parkinson’s disease (PD) patients. TMAO is a gut microbiota metabolite that can cross the blood–brain barrier and is strongly related to neuroinflammation. Neuroinflammation is one of the pathological drivers of PD. Herein, we investigated the effect of TMAO on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model mice. TMAO pretreatment was given by adding 1.5% (w/v) TMAO to the drinking water of the mice for 21 days; then, the mice were administered MPTP (20 mg/kg, i.p.) four times a day to construct an acute PD model. Their serum TMAO concentrations, motor function, dopaminergic network integrity, and neuroinflammation were then assayed. The results showed that TMAO partly aggravated the motor dysfunction of the PD mice. Although TMAO had no effect on the dopaminergic neurons, TH protein content, and striatal DA level in the PD mice, it significantly reduced the striatal 5-HT levels and aggravated the metabolism of DA and 5-HT. Meanwhile, TMAO significantly activated glial cells in the striatum and the hippocampi of the PD mice and promoted the release of inflammatory cytokines in the hippocampus. In summary, higher-circulating TMAO had adverse effects on the motor capacity, striatum neurotransmitters, and striatal and hippocampal neuroinflammation in PD mice. Full article
(This article belongs to the Section Neurodegenerative Diseases)
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27 pages, 1281 KiB  
Review
Therapeutic Strategies to Ameliorate Neuronal Damage in Epilepsy by Regulating Oxidative Stress, Mitochondrial Dysfunction, and Neuroinflammation
by Sahithi Madireddy and Samskruthi Madireddy
Brain Sci. 2023, 13(5), 784; https://doi.org/10.3390/brainsci13050784 - 11 May 2023
Cited by 23 | Viewed by 5830
Abstract
Epilepsy is a central nervous system disorder involving spontaneous and recurring seizures that affects 50 million individuals globally. Because approximately one-third of patients with epilepsy do not respond to drug therapy, the development of new therapeutic strategies against epilepsy could be beneficial. Oxidative [...] Read more.
Epilepsy is a central nervous system disorder involving spontaneous and recurring seizures that affects 50 million individuals globally. Because approximately one-third of patients with epilepsy do not respond to drug therapy, the development of new therapeutic strategies against epilepsy could be beneficial. Oxidative stress and mitochondrial dysfunction are frequently observed in epilepsy. Additionally, neuroinflammation is increasingly understood to contribute to the pathogenesis of epilepsy. Mitochondrial dysfunction is also recognized for its contributions to neuronal excitability and apoptosis, which can lead to neuronal loss in epilepsy. This review focuses on the roles of oxidative damage, mitochondrial dysfunction, NAPDH oxidase, the blood–brain barrier, excitotoxicity, and neuroinflammation in the development of epilepsy. We also review the therapies used to treat epilepsy and prevent seizures, including anti-seizure medications, anti-epileptic drugs, anti-inflammatory therapies, and antioxidant therapies. In addition, we review the use of neuromodulation and surgery in the treatment of epilepsy. Finally, we present the role of dietary and nutritional strategies in the management of epilepsy, including the ketogenic diet and the intake of vitamins, polyphenols, and flavonoids. By reviewing available interventions and research on the pathophysiology of epilepsy, this review points to areas of further development for therapies that can manage epilepsy. Full article
(This article belongs to the Special Issue Recent Advances in Pathophysiology and Therapeutic Approaches in Epilepsy)
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12 pages, 1087 KiB  
Article
Abnormal Brain Structure Is Associated with Social and Communication Deficits in Children with Autism Spectrum Disorder: A Voxel-Based Morphometry Analysis
by Ming-Xiang Xu and Xing-Da Ju
Brain Sci. 2023, 13(5), 779; https://doi.org/10.3390/brainsci13050779 - 10 May 2023
Cited by 10 | Viewed by 4845
Abstract
Structural magnetic resonance imaging (sMRI) studies have shown abnormalities in the brain structure of ASD patients, but the relationship between structural changes and social communication problems is still unclear. This study aims to explore the structural mechanisms of clinical dysfunction in the brain [...] Read more.
Structural magnetic resonance imaging (sMRI) studies have shown abnormalities in the brain structure of ASD patients, but the relationship between structural changes and social communication problems is still unclear. This study aims to explore the structural mechanisms of clinical dysfunction in the brain of ASD children through voxel-based morphometry (VBM). After screening T1 structural images from the Autism Brain Imaging Data Exchange (ABIDE) database, 98 children aged 8–12 years old with ASD were matched with 105 children aged 8–12 years old with typical development (TD). Firstly, this study compared the differences in gray matter volume (GMV) between the two groups. Then, this study evaluated the relationship between GMV and the subtotal score of communications and social interaction on the Autism Diagnostic Observation Schedule (ADOS) in ASD children. Research has found that abnormal brain structures in ASD include the midbrain, pontine, bilateral hippocampus, left parahippocampal gyrus, left superior temporal gyrus, left temporal pole, left middle temporal gyrus and left superior occipital gyrus. In addition, in ASD children, the subtotal score of communications and social interaction on the ADOS were only significantly positively correlated with GMV in the left hippocampus, left superior temporal gyrus and left middle temporal gyrus. In summary, the gray matter structure of ASD children is abnormal, and different clinical dysfunction in ASD children is related to structural abnormalities in specific regions. Full article
(This article belongs to the Section Behavioral Neuroscience)
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10 pages, 878 KiB  
Review
The Role of The Rostral Ventromedial Medulla in Stress Responses
by Marco Pagliusi, Jr. and Felipe V. Gomes
Brain Sci. 2023, 13(5), 776; https://doi.org/10.3390/brainsci13050776 - 9 May 2023
Cited by 9 | Viewed by 4809
Abstract
The rostral ventromedial medulla (RVM) is a brainstem structure critical for the descending pain modulation system involved in both pain facilitation and inhibition through its projection to the spinal cord. Since the RVM is well connected with pain- and stress-engaged brain structures, such [...] Read more.
The rostral ventromedial medulla (RVM) is a brainstem structure critical for the descending pain modulation system involved in both pain facilitation and inhibition through its projection to the spinal cord. Since the RVM is well connected with pain- and stress-engaged brain structures, such as the anterior cingulate cortex, nucleus accumbens, and amygdala, its involvement in stress responses has become a matter of great interest. While chronic stress has been proposed as a trigger of pain chronification and related psychiatric comorbidities due to maladaptive stress responses, acute stress triggers analgesia and other adaptative responses. Here we reviewed and highlighted the critical role of the RVM in stress responses, mainly in acute stress-induced analgesia (SIA) and chronic stress-induced hyperalgesia (SIH), providing insights into pain chronification processes and comorbidity between chronic pain and psychiatric disorders. Full article
(This article belongs to the Section Behavioral Neuroscience)
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15 pages, 337 KiB  
Review
Mood Stabilizers of First and Second Generation
by Janusz K. Rybakowski
Brain Sci. 2023, 13(5), 741; https://doi.org/10.3390/brainsci13050741 - 29 Apr 2023
Cited by 13 | Viewed by 5054
Abstract
The topic of this narrative review is mood stabilizers. First, the author’s definition of mood-stabilizing drugs is provided. Second, mood-stabilizing drugs meeting this definition that have been employed until now are described. They can be classified into two generations based on the chronology [...] Read more.
The topic of this narrative review is mood stabilizers. First, the author’s definition of mood-stabilizing drugs is provided. Second, mood-stabilizing drugs meeting this definition that have been employed until now are described. They can be classified into two generations based on the chronology of their introduction into the psychiatric armamentarium. First-generation mood stabilizers (FGMSs), such as lithium, valproates, and carbamazepine, were introduced in the 1960s and 1970s. Second-generation mood stabilizers (SGMSs) started in 1995, with a discovery of the mood-stabilizing properties of clozapine. The SGMSs include atypical antipsychotics, such as clozapine, olanzapine, quetiapine, aripiprazole, and risperidone, as well as a new anticonvulsant drug, lamotrigine. Recently, as a candidate for SGMSs, a novel antipsychotic, lurasidone, has been suggested. Several other atypical antipsychotics, anticonvulsants, and memantine showed some usefulness in the treatment and prophylaxis of bipolar disorder; however, they do not fully meet the author’s criteria for mood stabilizers. The article presents clinical experiences with mood stabilizers of the first and second generations and with “insufficient” ones. Further, current suggestions for their use in preventing recurrences of bipolar mood disorder are provided. Full article
(This article belongs to the Special Issue Neuropsychopharmacology in Mood Disorders)
20 pages, 4690 KiB  
Article
Differentiated Neurons Are More Vulnerable to Organophosphate and Carbamate Neurotoxicity than Undifferentiated Neurons Due to the Induction of Redox Stress and Accumulate Oxidatively-Damaged Proteins
by Anusha W. Mudyanselage, Buddhika C. Wijamunige, Artur Kocon and Wayne G. Carter
Brain Sci. 2023, 13(5), 728; https://doi.org/10.3390/brainsci13050728 - 26 Apr 2023
Cited by 8 | Viewed by 1875
Abstract
Organophosphate (OP) and carbamate pesticides are toxic to pests through targeted inhibition of acetylcholinesterase (AChE). However, OPs and carbamates may be harmful to non-target species including humans and could induce developmental neurotoxicity if differentiated or differentiating neurons are particularly vulnerable to neurotoxicant exposures. [...] Read more.
Organophosphate (OP) and carbamate pesticides are toxic to pests through targeted inhibition of acetylcholinesterase (AChE). However, OPs and carbamates may be harmful to non-target species including humans and could induce developmental neurotoxicity if differentiated or differentiating neurons are particularly vulnerable to neurotoxicant exposures. Hence, this study compared the neurotoxicity of OPs, chlorpyrifos-oxon (CPO), and azamethiphos (AZO) and the carbamate pesticide, aldicarb, to undifferentiated versus differentiated SH-SY5Y neuroblastoma cells. OP and carbamate concentration-response curves for cell viability were undertaken using 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays and cellular bioenergetic capacity assessed via quantitation of cellular ATP levels. Concentration-response curves for inhibition of cellular AChE activity were also generated and the production of reactive oxygen species (ROS) was monitored using a 2′,7′-dichlorofluorescein diacetate (DCFDA) assay. The OPs and aldicarb reduced cell viability, cellular ATP levels, and neurite outgrowth in a concentration-dependent fashion, from a threshold concentration of ≥10 µM. Neurotoxic potency was in the order AZO > CPO > aldicarb for undifferentiated cells but CPO > AZO > aldicarb for differentiated cells and this toxic potency of CPO reflected its more extensive induction of reactive oxygen species (ROS) and generation of carbonylated proteins that were characterized by western blotting. Hence, the relative neurotoxicity of the OPs and aldicarb in part reflects non-cholinergic mechanisms that are likely to contribute to developmental neurotoxicity. Full article
(This article belongs to the Special Issue The Neurotoxicity of Pesticides)
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22 pages, 5499 KiB  
Review
A Comprehensive Review of Physical Therapy Interventions for Stroke Rehabilitation: Impairment-Based Approaches and Functional Goals
by Jawaria Shahid, Ayesha Kashif and Muhammad Kashif Shahid
Brain Sci. 2023, 13(5), 717; https://doi.org/10.3390/brainsci13050717 - 25 Apr 2023
Cited by 25 | Viewed by 24995
Abstract
Stroke is the fourth leading cause of mortality and is estimated to be one of the major reasons for long-lasting disability worldwide. There are limited studies that describe the application of physical therapy interventions to prevent disabilities in stroke survivors and promote recovery [...] Read more.
Stroke is the fourth leading cause of mortality and is estimated to be one of the major reasons for long-lasting disability worldwide. There are limited studies that describe the application of physical therapy interventions to prevent disabilities in stroke survivors and promote recovery after a stroke. In this review, we have described a wide range of interventions based on impairments, activity limitations, and goals in recovery during different stages of a stroke. This article mainly focuses on stroke rehabilitation tactics, including those for sensory function impairments, motor learning programs, hemianopia and unilateral neglect, flexibility and joint integrity, strength training, hypertonicity, postural control, and gait training. We conclude that, aside from medicine, stroke rehabilitation must address specific functional limitations to allow for group activities and superior use of a hemiparetic extremity. Medical doctors are often surprised by the variety of physiotherapeutic techniques available; they are unfamiliar with the approaches of researchers such as Bobath, Coulter, and Brunnstrom, among others, as well as the scientific reasoning behind these techniques. Full article
(This article belongs to the Section Neurorehabilitation)
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20 pages, 2172 KiB  
Article
Research and Diagnostic Algorithmic Rules (RADAR) and RADAR Plots for the First Episode of Major Depressive Disorder: Effects of Childhood and Recent Adverse Experiences on Suicidal Behaviors, Neurocognition and Phenome Features
by Michael Maes and Abbas F. Almulla
Brain Sci. 2023, 13(5), 714; https://doi.org/10.3390/brainsci13050714 - 24 Apr 2023
Cited by 13 | Viewed by 2324
Abstract
Recent studies have proposed valid precision models and valid Research and Diagnostic Algorithmic Rules (RADAR) for recurrent major depressive disorder (MDD). The aim of the current study was to construct precision models and RADAR scores in patients experiencing first-episode MDD and to examine [...] Read more.
Recent studies have proposed valid precision models and valid Research and Diagnostic Algorithmic Rules (RADAR) for recurrent major depressive disorder (MDD). The aim of the current study was to construct precision models and RADAR scores in patients experiencing first-episode MDD and to examine whether adverse childhood experiences (ACE) and negative life events (NLE) are associated with suicidal behaviors (SB), cognitive impairment, and phenome RADAR scores. This study recruited 90 patients with major depressive disorder (MDD) in an acute phase, of whom 71 showed a first-episode MDD (FEM), and 40 controls. We constructed RADAR scores for ACE; NLE encountered in the last year; SB; and severity of depression, anxiety, chronic fatigue, and physiosomatic symptoms using the Hamilton Depression and Anxiety Rating Scales and the FibroFatigue scale. The partial least squares analysis showed that in FEM, one latent vector (labeled the phenome of FEM) could be extracted from depressive, anxiety, fatigue, physiosomatic, melancholia, and insomnia symptoms, SB, and cognitive impairments. The latter were conceptualized as a latent vector extracted from the Verbal Fluency Test, the Mini-Mental State Examination, and ratings of memory and judgement, indicating a generalized cognitive decline (G-CoDe). We found that 60.8% of the variance in the FEM phenome was explained by the cumulative effects of NLE and ACE, in particular emotional neglect and, to a lesser extent, physical abuse. In conclusion, the RADAR scores and plots constructed here should be used in research and clinical settings, rather than the binary diagnosis of MDD based on the DSM-5 or ICD. Full article
(This article belongs to the Special Issue Anxious Brain: Stress Influence on the Nervous System)
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17 pages, 880 KiB  
Systematic Review
Exploring the Social Determinants of Health and Health Disparities in Traumatic Brain Injury: A Scoping Review
by Leslie W. Johnson and Isabella Diaz
Brain Sci. 2023, 13(5), 707; https://doi.org/10.3390/brainsci13050707 - 23 Apr 2023
Cited by 26 | Viewed by 4006
Abstract
Traumatic brain injury (TBI) is a global health concern, that can leave lasting physical, cognitive, and/or behavioral changes for many who sustain this type of injury. Because of the heterogeneity of this population, development of appropriate intervention tools can be difficult. Social determinants [...] Read more.
Traumatic brain injury (TBI) is a global health concern, that can leave lasting physical, cognitive, and/or behavioral changes for many who sustain this type of injury. Because of the heterogeneity of this population, development of appropriate intervention tools can be difficult. Social determinants of health (SDoH) are factors that may impact TBI incidence, recovery, and outcome. The purpose of this study is to describe and analyze the existing literature regarding the prevailing SDoH and health disparities (HDs) associated with TBI in adults. A scoping review, guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework was used to explore three electronic databases—PubMed, Medline, and CINAHL. Searches identified peer-reviewed empirical literature addressing aspects of SDoH and HDs related to TBI. A total of 123 records were identified and reduced to 27 studies based on inclusion criteria. Results revealed race/ethnicity was the most commonly reported SDoH impacting TBI, followed by an individual’s insurance status. Health disparities were noted to occur across the continuum of TBI, including TBI risk, acute hospitalization, rehabilitation, and recovery. The most frequently reported HD was that Whites are more likely to be discharged to inpatient rehabilitation compared to racial/ethnic minorities. Health disparities associated with TBI are most commonly associated with the race/ethnicity SDoH, though insurance status and socioeconomic status commonly influence health inequities as well. The additional need for evidence related to the impact of other, lesser researched, SDoH is discussed, as well as clinical implications that can be used to target intervention for at-risk groups using an individual’s known SDoH. Full article
(This article belongs to the Section Behavioral Neuroscience)
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30 pages, 2821 KiB  
Review
Analysis of IoT Security Challenges and Its Solutions Using Artificial Intelligence
by Tehseen Mazhar, Dhani Bux Talpur, Tamara Al Shloul, Yazeed Yasin Ghadi, Inayatul Haq, Inam Ullah, Khmaies Ouahada and Habib Hamam
Brain Sci. 2023, 13(4), 683; https://doi.org/10.3390/brainsci13040683 - 19 Apr 2023
Cited by 39 | Viewed by 8758
Abstract
The Internet of Things (IoT) is a well-known technology that has a significant impact on many areas, including connections, work, healthcare, and the economy. IoT has the potential to improve life in a variety of contexts, from smart cities to classrooms, by automating [...] Read more.
The Internet of Things (IoT) is a well-known technology that has a significant impact on many areas, including connections, work, healthcare, and the economy. IoT has the potential to improve life in a variety of contexts, from smart cities to classrooms, by automating tasks, increasing output, and decreasing anxiety. Cyberattacks and threats, on the other hand, have a significant impact on intelligent IoT applications. Many traditional techniques for protecting the IoT are now ineffective due to new dangers and vulnerabilities. To keep their security procedures, IoT systems of the future will need AI-efficient machine learning and deep learning. The capabilities of artificial intelligence, particularly machine and deep learning solutions, must be used if the next-generation IoT system is to have a continuously changing and up-to-date security system. IoT security intelligence is examined in this paper from every angle available. An innovative method for protecting IoT devices against a variety of cyberattacks is to use machine learning and deep learning to gain information from raw data. Finally, we discuss relevant research issues and potential next steps considering our findings. This article examines how machine learning and deep learning can be used to detect attack patterns in unstructured data and safeguard IoT devices. We discuss the challenges that researchers face, as well as potential future directions for this research area, considering these findings. Anyone with an interest in the IoT or cybersecurity can use this website’s content as a technical resource and reference. Full article
(This article belongs to the Special Issue Intelligent Neural Systems for Solving Real Problems)
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18 pages, 1224 KiB  
Systematic Review
The Use of Neurofeedback in Sports Training: Systematic Review
by Łukasz Rydzik, Wojciech Wąsacz, Tadeusz Ambroży, Norollah Javdaneh, Karolina Brydak and Marta Kopańska
Brain Sci. 2023, 13(4), 660; https://doi.org/10.3390/brainsci13040660 - 14 Apr 2023
Cited by 17 | Viewed by 8378
Abstract
Biofeedback training is a method commonly used in various fields of life, for example, in medicine, sports training or business. In recent studies, it has been shown that biofeedback, and neurofeedback, can affect the performance of professional athletes. Training based on the neurofeedback [...] Read more.
Biofeedback training is a method commonly used in various fields of life, for example, in medicine, sports training or business. In recent studies, it has been shown that biofeedback, and neurofeedback, can affect the performance of professional athletes. Training based on the neurofeedback method includes exercising the brain waves. The aim of the article is to evaluate the influence of neurofeedback training on the physical fitness of professional athletes representing various sports disciplines, such as judo, volleyball and soccer. Based on 10 scientific papers from various sources, including PubMed, the latest research on neurofeedback and its impact on athletes has been reviewed. On the basis of the literature review from 2012 to 2022 on the neurofeedback method in sports training, it can be stated that this type of practice has a significant impact on physical fitness and sports performance. This review comprised 10 research studies with 491 participants in the neurofeedback groups, and 62 participants in the control group. Two reviewers independently extracted data and evaluated the quality of the studies utilising the PEDro scale. Properly planned and conducted neurofeedback training affects stimulation and improvement of many variables (reducing stress levels, increasing the ability to self-control physiological factors, enhancing behavioural efficiency and meliorating the speed of reaction to a stimulus). Full article
(This article belongs to the Special Issue The Contribution of Cognitive Training on Sport and Physical Performance, and Vice Versa)
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17 pages, 4159 KiB  
Article
Intranasal Delivery of Gene-Edited Microglial Exosomes Improves Neurological Outcomes after Intracerebral Hemorrhage by Regulating Neuroinflammation
by Mengtian Guo, Xintong Ge, Conglin Wang, Zhenyu Yin, Zexi Jia, Tianpeng Hu, Meimei Li, Dong Wang, Zhaoli Han, Lu Wang, Xiangyang Xiong, Fanglian Chen and Ping Lei
Brain Sci. 2023, 13(4), 639; https://doi.org/10.3390/brainsci13040639 - 8 Apr 2023
Cited by 12 | Viewed by 2949
Abstract
Neural inflammatory response is a crucial pathological change in intracerebral hemorrhage (ICH) which accelerates the formation of perihematomal edema and aggravates neural cell death. Although surgical and drug treatments for ICH have advanced rapidly in recent years, therapeutic strategies that target and control [...] Read more.
Neural inflammatory response is a crucial pathological change in intracerebral hemorrhage (ICH) which accelerates the formation of perihematomal edema and aggravates neural cell death. Although surgical and drug treatments for ICH have advanced rapidly in recent years, therapeutic strategies that target and control neuroinflammation are still limited. Exosomes are important carriers for information transfer among cells. They have also been regarded as a promising therapeutic tool in translational medicine, with low immunogenicity, high penetration through the blood-brain barrier, and ease of modification. In our previous research, we have found that exogenous administration of miRNA-124-overexpressed microglial exosomes (Exo-124) are effective in improving post-injury cognitive impairment. From this, we evaluated the potential therapeutic effects of miRNA-124-enriched microglial exosomes on the ICH mice in the present study. We found that the gene-edited exosomes could attenuate neuro-deficits and brain edema, improve blood–brain barrier integrity, and reduce neural cell death. Moreover, the protective effect of Exo-124 was abolished in mice depleted of Gr-1+ myeloid cells. It suggested that the exosomes exerted their functions by limiting the infiltration of leukocyte into the brain, thus controlling neuroinflammation following the onset of ICH. In conclusion, our findings provided a promising therapeutic strategy for improving neuroinflammation in ICH. It also opens a new avenue for intranasal delivery of exosome therapy using miRNA-edited microglial exosomes. Full article
(This article belongs to the Special Issue Immunomodulation and Immunotherapy in Neurological Disorders)
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22 pages, 7257 KiB  
Article
Molecular Mechanisms of the Anti-Inflammatory Effects of Epigallocatechin 3-Gallate (EGCG) in LPS-Activated BV-2 Microglia Cells
by Ashley Payne, Equar Taka, Getinet M. Adinew and Karam F. A. Soliman
Brain Sci. 2023, 13(4), 632; https://doi.org/10.3390/brainsci13040632 - 7 Apr 2023
Cited by 14 | Viewed by 3644
Abstract
Chronic neuroinflammation is associated with many neurodegenerative diseases, such as Alzheimer’s. Microglia are the brain’s primary immune cells, and when activated, they release various proinflammatory cytokines. Several natural compounds with anti-inflammatory and antioxidant properties, such as epigallocatechin 3-gallate (EGCG), may provide a promising [...] Read more.
Chronic neuroinflammation is associated with many neurodegenerative diseases, such as Alzheimer’s. Microglia are the brain’s primary immune cells, and when activated, they release various proinflammatory cytokines. Several natural compounds with anti-inflammatory and antioxidant properties, such as epigallocatechin 3-gallate (EGCG), may provide a promising strategy for inflammation-related neurodegenerative diseases involving activated microglia cells. The objective of the current study was to examine the molecular targets underlying the anti-inflammatory effects of EGCG in activated microglia cells. BV-2 microglia cells were grown, stimulated, and treated with EGCG. Cytotoxicity and nitric oxide (NO) production were evaluated. Immunoassay, PCR array, and WES™ Technology were utilized to evaluate inflammatory, neuroprotective modulators as well as signaling pathways involved in the mechanistic action of neuroinflammation. Our findings showed that EGCG significantly inhibited proinflammatory mediator NO production in LPS-stimulated BV-2 microglia cells. In addition, ELISA analysis revealed that EGCG significantly decreases the release of proinflammatory cytokine IL-6 while it increases the release of TNF-α. PCR array analysis showed that EGCG downregulated MIF, CCL-2, and CSF2. It also upregulated IL-3, IL-11, and TNFS10. Furthermore, the analysis of inflammatory signaling pathways showed that EGCG significantly downregulated mRNA expression of mTOR, NF-κB2, STAT1, Akt3, CCL5, and SMAD3 while significantly upregulating the expression of mRNA of Ins2, Pld2, A20/TNFAIP3, and GAB1. Additionally, EGCG reduced the relative protein expression of NF-κB2, mTOR, and Akt3. These findings suggest that EGCG may be used for its anti-inflammatory effects to prevent neurodegenerative diseases. Full article
(This article belongs to the Special Issue Advances in Cell Therapy of Neurodegenerative Diseases)
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13 pages, 989 KiB  
Review
Microglia and Astrocytes Dysfunction and Key Neuroinflammation-Based Biomarkers in Parkinson’s Disease
by Kun Chen, Haoyang Wang, Iqra Ilyas, Arif Mahmood and Lijun Hou
Brain Sci. 2023, 13(4), 634; https://doi.org/10.3390/brainsci13040634 - 7 Apr 2023
Cited by 20 | Viewed by 4596
Abstract
Parkinson’s disease (PD) is the second most common neurodegenerative disease, with symptoms such as tremor, bradykinesia with rigidity, and depression appearing in the late stage of life. The key hallmark of PD is the loss or death of dopaminergic neurons in the region [...] Read more.
Parkinson’s disease (PD) is the second most common neurodegenerative disease, with symptoms such as tremor, bradykinesia with rigidity, and depression appearing in the late stage of life. The key hallmark of PD is the loss or death of dopaminergic neurons in the region substantia nigra pars compacta. Neuroinflammation plays a key role in the etiology of PD, and the contribution of immunity-related events spurred the researchers to identify anti-inflammatory agents for the treatment of PD. Neuroinflammation-based biomarkers have been identified for diagnosing PD, and many cellular and animal models have been used to explain the underlying mechanism; however, the specific cause of neuroinflammation remains uncertain, and more research is underway. So far, microglia and astrocyte dysregulation has been reported in PD. Patients with PD develop neural toxicity, inflammation, and inclusion bodies due to activated microglia and a-synuclein–induced astrocyte conversion into A1 astrocytes. Major phenotypes of PD appear in the late stage of life, so there is a need to identify key early-stage biomarkers for proper management and diagnosis. Studies are under way to identify key neuroinflammation-based biomarkers for early detection of PD. This review uses a constructive analysis approach by studying and analyzing different research studies focused on the role of neuroinflammation in PD. The review summarizes microglia, astrocyte dysfunction, neuroinflammation, and key biomarkers in PD. An approach that incorporates multiple biomarkers could provide more reliable diagnosis of PD. Full article
(This article belongs to the Special Issue Updates in Parkinson's Disease)
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13 pages, 785 KiB  
Article
Can Virtual Reality Cognitive Rehabilitation Improve Executive Functioning and Coping Strategies in Traumatic Brain Injury? A Pilot Study
by Rosaria De Luca, Mirjam Bonanno, Angela Marra, Carmela Rifici, Patrizia Pollicino, Angelo Caminiti, Milva Veronica Castorina, Andrea Santamato, Angelo Quartarone and Rocco Salvatore Calabrò
Brain Sci. 2023, 13(4), 578; https://doi.org/10.3390/brainsci13040578 - 29 Mar 2023
Cited by 9 | Viewed by 4216
Abstract
Executive dysfunction is among the most common and disabling facets of cognitive impairment following traumatic brain injury (TBI), and may include deficits in reasoning, planning, mental flexibility, some aspects of attention and orientation, awareness and behavior. Rehabilitation programs based on cognitive-behavioral approaches to [...] Read more.
Executive dysfunction is among the most common and disabling facets of cognitive impairment following traumatic brain injury (TBI), and may include deficits in reasoning, planning, mental flexibility, some aspects of attention and orientation, awareness and behavior. Rehabilitation programs based on cognitive-behavioral approaches to retrain planning and problem-solving and other executive deficits may improve such cognitive dysfunction. The purpose of this study is to investigate the effects of non-immersive virtual reality-based training to improve executive abilities and to reduce anxiety and depression symptoms in patients with TBI. Twenty patients with moderate to severe TBI were enrolled at our Neurorehabilitation Unit and divided to receive either the standard cognitive training or the virtual reality (VR) based cognitive training using the virtual reality rehabilitation system (VRRS-Evo). Each group received the same amount of rehabilitative training, including ROT (Reality Orientation Therapy) and Executive Training (ET), but using a different approach, i.e., a paper and pencil and an advanced approach. All patients were evaluated with a specific psychometric battery before (T0) and after the end (T1) of each program. Comparing pre- and post- treatment scores, in the VR-CT group, we found statistically significant differences in all administered outcome measures for cognitive and executive functioning, i.e., MoCA (p < 0.005), FAB (p < 0.005), TMT-A (p < 0.005), TMT-B (p < 0.005), TMT-BA (p < 0.001), and mood, i.e., HRS-D (p < 0.008). In the Conventional cognitive training (C-CT) group, we found a significant improvement only in MoCA (p < 0.03), FAB (p < 0.02) and in TMT-BA (p < 0.01). Coping strategies also improved, with better results in the VR-CT group. Our results suggest that VR rehabilitation, using the VRRS system, may be a valuable and motivational approach to improve visuo-executive abilities and coping strategies as well as mood in chronic TBI patients. Full article
(This article belongs to the Special Issue Robot-, Virtual Reality- and Sensor-Based Therapies Boosting Neuroplasticity in the Context of Motor and Cognitive Neurorehabilitation: Current State of the Art and Applications)
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22 pages, 912 KiB  
Review
Sleep Deprivation and Insomnia in Adolescence: Implications for Mental Health
by Sara Uccella, Ramona Cordani, Federico Salfi, Maurizio Gorgoni, Serena Scarpelli, Angelo Gemignani, Pierre Alexis Geoffroy, Luigi De Gennaro, Laura Palagini, Michele Ferrara and Lino Nobili
Brain Sci. 2023, 13(4), 569; https://doi.org/10.3390/brainsci13040569 - 28 Mar 2023
Cited by 24 | Viewed by 19815
Abstract
Sleep changes significantly throughout the human lifespan. Physiological modifications in sleep regulation, in common with many mammals (especially in the circadian rhythms), predispose adolescents to sleep loss until early adulthood. Adolescents are one-sixth of all human beings and are at high risk for [...] Read more.
Sleep changes significantly throughout the human lifespan. Physiological modifications in sleep regulation, in common with many mammals (especially in the circadian rhythms), predispose adolescents to sleep loss until early adulthood. Adolescents are one-sixth of all human beings and are at high risk for mental diseases (particularly mood disorders) and self-injury. This has been attributed to the incredible number of changes occurring in a limited time window that encompasses rapid biological and psychosocial modifications, which predispose teens to at-risk behaviors. Adolescents’ sleep patterns have been investigated as a biunivocal cause for potential damaging conditions, in which insufficient sleep may be both a cause and a consequence of mental health problems. The recent COVID-19 pandemic in particular has made a detrimental contribution to many adolescents’ mental health and sleep quality. In this review, we aim to summarize the knowledge in the field and to explore implications for adolescents’ (and future adults’) mental and physical health, as well as to outline potential strategies of prevention. Full article
(This article belongs to the Special Issue Effects of Sleep Deprivation on Cognition, Emotion, and Behavior)
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24 pages, 2414 KiB  
Review
Exploring Monocytes-Macrophages in Immune Microenvironment of Glioblastoma for the Design of Novel Therapeutic Strategies
by Matías Daniel Caverzán, Lucía Beaugé, Paula Martina Oliveda, Bruno Cesca González, Eugenia Micaela Bühler and Luis Exequiel Ibarra
Brain Sci. 2023, 13(4), 542; https://doi.org/10.3390/brainsci13040542 - 24 Mar 2023
Cited by 11 | Viewed by 3889
Abstract
Gliomas are primary malignant brain tumors. These tumors seem to be more and more frequent, not only because of a true increase in their incidence, but also due to the increase in life expectancy of the general population. Among gliomas, malignant gliomas and [...] Read more.
Gliomas are primary malignant brain tumors. These tumors seem to be more and more frequent, not only because of a true increase in their incidence, but also due to the increase in life expectancy of the general population. Among gliomas, malignant gliomas and more specifically glioblastomas (GBM) are a challenge in their diagnosis and treatment. There are few effective therapies for these tumors, and patients with GBM fare poorly, even after aggressive surgery, chemotherapy, and radiation. Over the last decade, it is now appreciated that these tumors are composed of numerous distinct tumoral and non-tumoral cell populations, which could each influence the overall tumor biology and response to therapies. Monocytes have been proved to actively participate in tumor growth, giving rise to the support of tumor-associated macrophages (TAMs). In GBM, TAMs represent up to one half of the tumor mass cells, including both infiltrating macrophages and resident brain microglia. Infiltrating macrophages/monocytes constituted ~ 85% of the total TAM population, they have immune functions, and they can release a wide array of growth factors and cytokines in response to those factors produced by tumor and non-tumor cells from the tumor microenvironment (TME). A brief review of the literature shows that this cell population has been increasingly studied in GBM TME to understand its role in tumor progression and therapeutic resistance. Through the knowledge of its biology and protumoral function, the development of therapeutic strategies that employ their recruitment as well as the modulation of their immunological phenotype, and even the eradication of the cell population, can be harnessed for therapeutic benefit. This revision aims to summarize GBM TME and localization in tumor niches with special focus on TAM population, its origin and functions in tumor progression and resistance to conventional and experimental GBM treatments. Moreover, recent advances on the development of TAM cell targeting and new cellular therapeutic strategies based on monocyte/macrophages recruitment to eradicate GBM are discussed as complementary therapeutics. Full article
(This article belongs to the Special Issue Advances in the Development of New Drugs and Treatment Targets for Brain Cancers)
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13 pages, 653 KiB  
Review
Preventive Strategies for Cognitive Decline and Dementia: Benefits of Aerobic Physical Activity, Especially Open-Skill Exercise
by Takao Yamasaki
Brain Sci. 2023, 13(3), 521; https://doi.org/10.3390/brainsci13030521 - 21 Mar 2023
Cited by 22 | Viewed by 7830
Abstract
As there is no curative treatment for dementia, including Alzheimer’s disease (AD), it is important to establish an optimal nonpharmaceutical preventive intervention. Physical inactivity is a representative modifiable risk factor for dementia, especially for AD in later life (>65 years). As physical activity [...] Read more.
As there is no curative treatment for dementia, including Alzheimer’s disease (AD), it is important to establish an optimal nonpharmaceutical preventive intervention. Physical inactivity is a representative modifiable risk factor for dementia, especially for AD in later life (>65 years). As physical activity and exercise are inexpensive and easy to initiate, they may represent an effective nonpharmaceutical intervention for the maintenance of cognitive function. Several studies have reported that physical activity and exercise interventions are effective in preventing cognitive decline and dementia. This review outlines the effects of physical activity and exercise-associated interventions in older adults with and without cognitive impairment and subsequently summarizes their possible mechanisms. Furthermore, this review describes the differences between two types of physical exercise—open-skill exercise (OSE) and closed-skill exercise (CSE)—in terms of their effects on cognitive function. Aerobic physical activity and exercise interventions are particularly useful in preventing cognitive decline and dementia, with OSE exerting a stronger protective effect on cognitive functions than CSE. Therefore, the need to actively promote physical activity and exercise interventions worldwide is emphasized. Full article
(This article belongs to the Special Issue Advances in Research on Brain Health and Dementia: Prevention and Early Detection of Cognitive Decline and Dementia)
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14 pages, 2350 KiB  
Article
Altered Postcentral Connectivity after Sleep Deprivation Correlates to Impaired Risk Perception: A Resting-State Functional Magnetic Resonance Imaging Study
by Jie Chen, Xinxin Gong, Letong Wang, Mengmeng Xu, Xiao Zhong, Ziyi Peng, Tao Song, Lin Xu, Jie Lian, Yongcong Shao and Xiechuan Weng
Brain Sci. 2023, 13(3), 514; https://doi.org/10.3390/brainsci13030514 - 20 Mar 2023
Cited by 8 | Viewed by 2497
Abstract
Background: Previous studies revealed that sleep deprivation (SD) impairs risk perception and leads to poor decision-making efficiency. However, how risk perception is related to brain regions’ communication after SD has not been elucidated. In this study, we investigated the neuropsychological mechanisms of SD-impaired [...] Read more.
Background: Previous studies revealed that sleep deprivation (SD) impairs risk perception and leads to poor decision-making efficiency. However, how risk perception is related to brain regions’ communication after SD has not been elucidated. In this study, we investigated the neuropsychological mechanisms of SD-impaired risk perception. Methods: Nineteen healthy male adults were recruited and underwent resting-state functional magnetic resonance imaging during a state of rested wakefulness and after nearly 36 h of total SD. They then completed the balloon analog risk task, which was used to measure the risk perception ability of risky decision-making. Regional homogeneity (ReHo) and voxel-wise functional connectivity were used to investigate neurobiological changes caused by SD. Correlation analysis was used to investigate the relationship between changes in ReHo, function, and risk perception. Results: At the behavioral level, risk perception decreased after 36 h of SD. At the neural level, SD induced a significant increase in ReHo in the right postcentral gyrus and was positively correlated with risk perception changes. The functional connectivity between the right postcentral gyrus, left medial temporal gyrus, and right inferior temporal gyrus was enhanced. Critically, increased right postcentral gyrus and right inferior temporal gyrus connectivity positively correlated with changes in risk perception. Conclusions: SD impairs the risk perception associated with altered postcentral connectivity. The brain requires more energy to process and integrate sensory and perceptual information after SD, which may be one possible reason for decreased risk perception ability after SD. Full article
(This article belongs to the Special Issue Effects of Sleep Deprivation on Cognition, Emotion, and Behavior)
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15 pages, 4004 KiB  
Review
Current Advances in Papillary Craniopharyngioma: State-Of-The-Art Therapies and Overview of the Literature
by Gianpaolo Jannelli, Francesco Calvanese, Luca Paun, Gerald Raverot and Emmanuel Jouanneau
Brain Sci. 2023, 13(3), 515; https://doi.org/10.3390/brainsci13030515 - 20 Mar 2023
Cited by 10 | Viewed by 2256
Abstract
Craniopharyngiomas are commonly classified as low-grade tumors, although they may harbor a malignant behavior due to their high rate of recurrence and long-term morbidity. Craniopharyngiomas are classically distinguished into two histological types (adamantinomatous and papillary), which have been recently considered by the WHO [...] Read more.
Craniopharyngiomas are commonly classified as low-grade tumors, although they may harbor a malignant behavior due to their high rate of recurrence and long-term morbidity. Craniopharyngiomas are classically distinguished into two histological types (adamantinomatous and papillary), which have been recently considered by the WHO classification of CNS tumors as two independent entities, due to different epidemiological, radiological, histopathological, and genetic patterns. With regard to papillary craniopharyngioma, a BRAF V600 mutation is detected in 95% of cases. This genetic feature is opening new frontiers in the treatment of these tumors using an adjuvant or, in selected cases, a neo-adjuvant approach. In this article, we present an overview of the more recent literature, focusing on the specificities and the role of oncological treatment in the management of papillary craniopharyngiomas. Based on our research and experience, we strongly suggest a multimodal approach combining clinical, endocrinological, radiological, histological, and oncological findings in both preoperative workup and postoperative follow up to define a roadmap integrating every aspect of this challenging condition. Full article
(This article belongs to the Special Issue Advances in Diagnosis and Treatment of Brain Tumors and Nervous System Tumors)
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20 pages, 1433 KiB  
Article
Exploring Whether Iron Sequestration within the CNS of Patients with Alzheimer’s Disease Causes a Functional Iron Deficiency That Advances Neurodegeneration
by Steven M. LeVine, Sheila Tsau and Sumedha Gunewardena
Brain Sci. 2023, 13(3), 511; https://doi.org/10.3390/brainsci13030511 - 18 Mar 2023
Cited by 10 | Viewed by 3249
Abstract
The involvement of iron in the pathogenesis of Alzheimer’s disease (AD) may be multifaceted. Besides potentially inducing oxidative damage, the bioavailability of iron may be limited within the central nervous system, creating a functionally iron-deficient state. By comparing staining results from baseline and [...] Read more.
The involvement of iron in the pathogenesis of Alzheimer’s disease (AD) may be multifaceted. Besides potentially inducing oxidative damage, the bioavailability of iron may be limited within the central nervous system, creating a functionally iron-deficient state. By comparing staining results from baseline and modified iron histochemical protocols, iron was found to be more tightly bound within cortical sections from patients with high levels of AD pathology compared to subjects with a diagnosis of something other than AD. To begin examining whether the bound iron could cause a functional iron deficiency, a protein-coding gene expression dataset of initial, middle, and advanced stages of AD from olfactory bulb tissue was analyzed for iron-related processes with an emphasis on anemia-related changes in initial AD to capture early pathogenic events. Indeed, anemia-related processes had statistically significant alterations, and the significance of these changes exceeded those for AD-related processes. Other changes in patients with initial AD included the expressions of transcripts with iron-responsive elements and for genes encoding proteins for iron transport and mitochondrial-related processes. In the latter category, there was a decreased expression for the gene encoding pitrilysin metallopeptidase 1 (PITRM1). Other studies have shown that PITRM1 has an altered activity in patients with AD and is associated with pathological changes in this disease. Analysis of a gene expression dataset from PITRM1-deficient or sufficient organoids also revealed statistically significant changes in anemia-like processes. These findings, together with supporting evidence from the literature, raise the possibility that a pathogenic mechanism of AD could be a functional deficiency of iron contributing to neurodegeneration. Full article
(This article belongs to the Special Issue Cellular and Molecular Basis of Neurodegenerative Disease)
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16 pages, 2875 KiB  
Systematic Review
Cerebrolysin in Patients with TBI: Systematic Review and Meta-Analysis
by Konrad Jarosz, Klaudyna Kojder, Agata Andrzejewska, Joanna Solek-Pastuszka and Anna Jurczak
Brain Sci. 2023, 13(3), 507; https://doi.org/10.3390/brainsci13030507 - 17 Mar 2023
Cited by 10 | Viewed by 4197
Abstract
TBI (traumatic brain injury) is one of the most common causes of deaths and failure to return to society according to the latest statistics. Cerebrolysin is a drug approved for use in patients diagnosed with TBI. It is a mixture of neuropeptides derived [...] Read more.
TBI (traumatic brain injury) is one of the most common causes of deaths and failure to return to society according to the latest statistics. Cerebrolysin is a drug approved for use in patients diagnosed with TBI. It is a mixture of neuropeptides derived from purified porcine brain proteins and multiple experimental studies have proven its neuroprotective and neurorestorative properties both in vitro and in vivo. In our meta-analysis, we analyze the latest clinical study reports on the use of Cerebrolysin in patients with TBI. The authors searched the databases: Pub Med, Cinahl, Web Of Science, and Embase from database inception until 11th July 2022. Ten clinical studies were eligible and included in the final analysis, including both retrospective and prospective studies of 8749 patients. Treatment with Cerebrolysin was associated with a statistically significant change in GCS and GOS. Mortality of any cause and the length of stay was not affected by the treatment. Our findings support and confirm the beneficial effects of Cerebrolysin treatment on the clinical outcome of patients after TBI. Further multi-center studies to optimize dosing and time of administration should be conducted. Full article
(This article belongs to the Section Neurorehabilitation)
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26 pages, 441 KiB  
Review
Among Gerontogens, Heavy Metals Are a Class of Their Own: A Review of the Evidence for Cellular Senescence
by Samuel T. Vielee and John P. Wise, Jr.
Brain Sci. 2023, 13(3), 500; https://doi.org/10.3390/brainsci13030500 - 16 Mar 2023
Cited by 9 | Viewed by 2818
Abstract
Advancements in modern medicine have improved the quality of life across the globe and increased the average lifespan of our population by multiple decades. Current estimates predict by 2030, 12% of the global population will reach a geriatric age and live another 3–4 [...] Read more.
Advancements in modern medicine have improved the quality of life across the globe and increased the average lifespan of our population by multiple decades. Current estimates predict by 2030, 12% of the global population will reach a geriatric age and live another 3–4 decades. This swelling geriatric population will place critical stress on healthcare infrastructures due to accompanying increases in age-related diseases and comorbidities. While much research focused on long-lived individuals seeks to answer questions regarding how to age healthier, there is a deficit in research investigating what aspects of our lives accelerate or exacerbate aging. In particular, heavy metals are recognized as a significant threat to human health with links to a plethora of age-related diseases, and have widespread human exposures from occupational, medical, or environmental settings. We believe heavy metals ought to be classified as a class of gerontogens (i.e., chemicals that accelerate biological aging in cells and tissues). Gerontogens may be best studied through their effects on the “Hallmarks of Aging”, nine physiological hallmarks demonstrated to occur in aged cells, tissues, and bodies. Evidence suggests that cellular senescence—a permanent growth arrest in cells—is one of the most pertinent hallmarks of aging and is a useful indicator of aging in tissues. Here, we discuss the roles of heavy metals in brain aging. We briefly discuss brain aging in general, then expand upon observations for heavy metals contributing to age-related neurodegenerative disorders. We particularly emphasize the roles and observations of cellular senescence in neurodegenerative diseases. Finally, we discuss the observations for heavy metals inducing cellular senescence. The glaring lack of knowledge about gerontogens and gerontogenic mechanisms necessitates greater research in the field, especially in the context of the global aging crisis. Full article
(This article belongs to the Special Issue Advance in Study of Neurotoxic Chemicals in the Environment)
21 pages, 2801 KiB  
Review
Biological Factors Underpinning Suicidal Behaviour: An Update
by Maya N. Abou Chahla, Mahmoud I. Khalil, Stefano Comai, Lena Brundin, Sophie Erhardt and Gilles J. Guillemin
Brain Sci. 2023, 13(3), 505; https://doi.org/10.3390/brainsci13030505 - 16 Mar 2023
Cited by 11 | Viewed by 4751
Abstract
Suicide, a global health burden, represents the 17th leading cause of death worldwide (1.3%), but the 4th among young people aged between 15 and 29 years of age, according to World Health Organization (WHO), 2019. Suicidal behaviour is a complex, multi-factorial, polygenic and [...] Read more.
Suicide, a global health burden, represents the 17th leading cause of death worldwide (1.3%), but the 4th among young people aged between 15 and 29 years of age, according to World Health Organization (WHO), 2019. Suicidal behaviour is a complex, multi-factorial, polygenic and independent mental health problem caused by a combination of alterations and dysfunctions of several biological pathways and disruption of normal mechanisms in brain regions that remain poorly understood and need further investigation to be deciphered. Suicide complexity and unpredictability gained international interest as a field of research. Several studies have been conducted at the neuropathological, inflammatory, genetic, and molecular levels to uncover the triggers behind suicidal behaviour and develop convenient and effective therapeutic or at least preventive procedures. This review aims to summarise and focus on current knowledge of diverse biological pathways involved in the neurobiology of suicidal behaviour, and briefly highlights future potential therapeutic pathways to prevent or even treat this significant public health problem. Full article
(This article belongs to the Section Behavioral Neuroscience)
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18 pages, 351 KiB  
Article
Oxidative Stress Biomarkers among Schizophrenia Inpatients
by Magdalena Więdłocha, Natalia Zborowska, Piotr Marcinowicz, Weronika Dębowska, Marta Dębowska, Anna Zalewska, Mateusz Maciejczyk, Napoleon Waszkiewicz and Agata Szulc
Brain Sci. 2023, 13(3), 490; https://doi.org/10.3390/brainsci13030490 - 14 Mar 2023
Cited by 14 | Viewed by 2453
Abstract
Background. Finding the associations between schizophrenia symptoms and the biomarkers of inflammation, oxidative stress and the kynurenine pathway may lead to the individualization of treatment and increase its effectiveness. Methods. The study group included 82 schizophrenia inpatients. The Positive and Negative Symptoms Scale [...] Read more.
Background. Finding the associations between schizophrenia symptoms and the biomarkers of inflammation, oxidative stress and the kynurenine pathway may lead to the individualization of treatment and increase its effectiveness. Methods. The study group included 82 schizophrenia inpatients. The Positive and Negative Symptoms Scale (PANSS), the Brief Assessment of Cognition in Schizophrenia (BACS) and the Calgary Depression in Schizophrenia Scale were used for symptom evaluation. Biochemical analyses included oxidative stress parameters and brain-derived neurotrophic factor (BDNF). Results. Linear models revealed the following: (1) malondiadehyde (MDA), N-formylkynurenine (N-formKYN), advanced oxidation protein products (AOPP), advanced glycation end-products of proteins (AGE) and total oxidative status (TOS) levels are related to the PANSS-total score; (2) MDA, reduced glutathione (GSH) and BDNF levels are related to the PANSS-negative score; (3) TOS and kynurenine (KYN) levels are related to the PANSS-positive score; (4) levels of total antioxidant status (TAS) and AOPP along with the CDSS score are related to the BACS-total score; (5) TAS and N-formKYN levels are related to the BACS-working memory score. Conclusions. Oxidative stress biomarkers may be associated with the severity of schizophrenia symptoms in positive, negative and cognitive dimensions. The identification of biochemical markers associated with the specific symptom clusters may increase the understanding of biochemical profiles in schizophrenia patients. Full article
(This article belongs to the Special Issue Psychopharmacology and Biological Studies of Psychosis)
23 pages, 1476 KiB  
Review
An Analysis of Deep Learning Models in SSVEP-Based BCI: A Survey
by Dongcen Xu, Fengzhen Tang, Yiping Li, Qifeng Zhang and Xisheng Feng
Brain Sci. 2023, 13(3), 483; https://doi.org/10.3390/brainsci13030483 - 13 Mar 2023
Cited by 18 | Viewed by 5380
Abstract
The brain–computer interface (BCI), which provides a new way for humans to directly communicate with robots without the involvement of the peripheral nervous system, has recently attracted much attention. Among all the BCI paradigms, BCIs based on steady-state visual evoked potentials (SSVEPs) have [...] Read more.
The brain–computer interface (BCI), which provides a new way for humans to directly communicate with robots without the involvement of the peripheral nervous system, has recently attracted much attention. Among all the BCI paradigms, BCIs based on steady-state visual evoked potentials (SSVEPs) have the highest information transfer rate (ITR) and the shortest training time. Meanwhile, deep learning has provided an effective and feasible solution for solving complex classification problems in many fields, and many researchers have started to apply deep learning to classify SSVEP signals. However, the designs of deep learning models vary drastically. There are many hyper-parameters that influence the performance of the model in an unpredictable way. This study surveyed 31 deep learning models (2011–2023) that were used to classify SSVEP signals and analyzed their design aspects including model input, model structure, performance measure, etc. Most of the studies that were surveyed in this paper were published in 2021 and 2022. This survey is an up-to-date design guide for researchers who are interested in using deep learning models to classify SSVEP signals. Full article
(This article belongs to the Special Issue Brain-Computer Interfaces and Their Applications in Rehabilitation, Robotics, and Control of Human Brain States)
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