Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
3.7
4.7
Journals
Biomedicines
Special Issues
Brain Injury and Neurodegeneration: Molecular, Functional, and Translational Approach
share announcement

Brain Injury and Neurodegeneration: Molecular, Functional, and Translational Approach

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Neurobiology and Clinical Neuroscience".

Deadline for manuscript submissions: closed (31 October 2021) | Viewed by 85216

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editors

Dr. Kumar Vaibhav

E-Mail Website
Guest Editor
Department of Neurosurgery, Augusta University, Augusta, GA 30912, USA
Interests: traumatic brain injury; stroke; hemorrhages; Alzheimer’s disease; Parkinson’s disease; neuroinflammation; macrophages; neutrophils; t-cells; metabolism; cannabinoids; cannabinoid receptors; ischemic conditioning; edema; apoptosis; scavenging receptors; innate immune cells; innate lymphoid cells; cycloxygenase; mitochondria; RBCs; miRNA
Special Issues, Collections and Topics in MDPI journals
Dr. Meenakshi Ahluwalia

E-Mail Website
Co-Guest Editor
Department of Pathology, Augusta University, Augusta, GA 30912, USA
Interests: pathology; traumatic brain injury; macrophages; t-cells; cannabinoids; oxidative stress; pesticides; genetic alterations; genome sequencing; nucleic acid; imaging
Special Issues, Collections and Topics in MDPI journals
Dr. Pankaj Gaur

E-Mail Website
Co-Guest Editor
Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20007, USA
Interests: brain functions; traumatic brain injury; stroke; hemorrhages; alzheimer’s disease; Parkinson’s disease; Neuroinflammation
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

With the advance of neuroscience research, we have come across different kinds of brain pathologies such as traumatic brain injury (TBI), hypoxic/hypobaric insults, hemorrhages, stroke, and neurological disorders such as Parkinson’s and Alzheimer’s diseases. Any insult to brain (mild or acute) is multifactorial and initiates a cascade of inflammation, necrotic, and apoptotic pathways. It is well known that insult or injury to brain may lead to neurological disorders such as Alzheimer’s and Parkinson’s disease as time elapses and genetic or environmental factors play important roles in the progression of the disease. A large body of evidence has shown that oxidative stress, mitochondrial dysfunctions, protein aggregation and phosphorylation, excessive iron accumulation in brain, and neuro-inflammation play a pivotal role in neurodegeneration and brain injuries. The absence of a specific cure to limit injury progression after insult has persuaded the scientific community to study the mechanism behind the degenerative cascade and to explore different therapeutic strategies.

This Special Issue will provide a multidisciplinary platform for discussing pathology and intervention of brain disorders. This issue will emphasize the psychological, behavioral, inflammatory, and molecular mechanisms in the development of new preventive and therapeutic strategy to limit brain injury and neurodegenerative disorders. This issue accepts original high-quality research articles and reviews that are not yet published or sought for publication.

Potential topics include but are not limited to the following:

  • Molecular and histological alterations in an injured brain;
  • Behavioral changes in injured brain;
  • Hypoxic brain injury and role of vasculature;
  • Traumatic brain injury: mechanism and prevention;
  • Brain injury: emotional and psychological stress;
  • Parkinson’s and Alzheimer’s disease;
  • Neurodegeneration: Does it link to previous brain injury?
  • Brain insult and cognitive impairment;
  • Intracerebral hemorrhages and hypoxia;
  • Stroke-induced molecular and functional alterations;
  • Prevention of brain insult by natural molecules and pharmaceuticals;
  • Bioanalytical studies and receptor mediated mechanism of natural compounds for the prevention of different kind of brain injuries;
  • Mechanisms of action of pharmaceuticals and natural products targeting oxidative stress and neuroinflammation in injured brain;
  • Computational and genetic studies of brain injuries;
  • Brain injury: Protein misfolding and mitochondrial dysfunction.

Dr. Kumar Vaibhav
Guest Editor

Dr. Meenakshi Ahluwalia
Dr. Pankaj Gaur
Co-Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • brain injury
  • psychological stress
  • Parkinson’s disease
  • Alzheimer’s disease
  • stroke
  • neurodegeneration
  • hemorrhages
  • hypoxia
  • neuroinflammation
  • translational approaches
  • oxidative stress

Related Special Issue

Published Papers (19 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Editorial

Jump to: Research, Review, Other

5 pages, 230 KiB  
Editorial
Brain Injury and Neurodegeneration: Molecular, Functional, and Translational Approach
by Meenakshi Ahluwalia, Pankaj Gaur and Kumar Vaibhav
Biomedicines 2023, 11(7), 1947; https://doi.org/10.3390/biomedicines11071947 - 10 Jul 2023
Viewed by 882
Abstract
Recently, we have achieved substantial progress in our understanding of brain injury and neurodegeneration [...] Full article
(This article belongs to the Special Issue Brain Injury and Neurodegeneration: Molecular, Functional, and Translational Approach)

Research

Jump to: Editorial, Review, Other

13 pages, 13935 KiB  
Article
Relationship between Cognitive Dysfunction and Age-Related Variability in Oxidative Markers in Isolated Mitochondria of Alzheimer’s Disease Transgenic Mouse Brains
by Naoki Yoshida, Yugo Kato, Hirokatsu Takatsu and Koji Fukui
Biomedicines 2022, 10(2), 281; https://doi.org/10.3390/biomedicines10020281 - 26 Jan 2022
Cited by 13 | Viewed by 4725
Abstract
Many neurodegenerative disorders, including Alzheimer’s disease (AD), are strongly associated with the accumulation of oxidative damage. Transgenic animal models are commonly used to elucidate the pathogenic mechanism of AD. Beta amyloid (Aβ) and tau hyperphosphorylation are very famous hallmarks of AD and well-studied, [...] Read more.
Many neurodegenerative disorders, including Alzheimer’s disease (AD), are strongly associated with the accumulation of oxidative damage. Transgenic animal models are commonly used to elucidate the pathogenic mechanism of AD. Beta amyloid (Aβ) and tau hyperphosphorylation are very famous hallmarks of AD and well-studied, but the relationship between mitochondrial dysfunction and the onset and progression of AD requires further elucidation. In this study we used transgenic mice (the strain name is 5xFAD) at three different ages (3, 6, and 20 months old) as an AD model. Cognitive impairment in AD mice occurred in an age-dependent manner. Aβ1-40 expression significantly increased in an age-dependent manner in all brain regions with or without AD, and Aβ1-42 expression in the hippocampus increased at a young age. In a Western blot analysis using isolated mitochondria from three brain regions (cerebral cortex, cerebellum, and hippocampus), NMNAT-3 expression in the hippocampi of aged AD mice was significantly lower than that of young AD mice. SOD-2 expression in the hippocampi of AD mice was lower than for the age-matched controls. However, 3-NT expression in the hippocampi of AD mice was higher than for the age-matched controls. NQO-1 expression in the cerebral cortex of AD mice was higher than for the age-matched controls at every age that we examined. However, hippocampal NQO-1 expression in 6-month-old AD mice was significantly lower than in 3-month-old AD mice. These results indicate that oxidative stress in the hippocampi of AD mice is high compared to other brain regions and may induce mitochondrial dysfunction via oxidative damage. Protection of mitochondria from oxidative damage may be important to maintain cognitive function. Full article
(This article belongs to the Special Issue Brain Injury and Neurodegeneration: Molecular, Functional, and Translational Approach)
►▼ Show Figures

Figure 1

23 pages, 26272 KiB  
Article
Mitoquinone Helps Combat the Neurological, Cognitive, and Molecular Consequences of Open Head Traumatic Brain Injury at Chronic Time Point
by Muhammad Ali Haidar, Zaynab Shakkour, Chloe Barsa, Maha Tabet, Sarin Mekhjian, Hala Darwish, Mona Goli, Deborah Shear, Jignesh D. Pandya, Yehia Mechref, Riyad El Khoury, Kevin Wang and Firas Kobeissy
Biomedicines 2022, 10(2), 250; https://doi.org/10.3390/biomedicines10020250 - 24 Jan 2022
Cited by 9 | Viewed by 4967
Abstract
Traumatic brain injury (TBI) is a heterogeneous disease in its origin, neuropathology, and prognosis, with no FDA-approved treatments. The pathology of TBI is complicated and not sufficiently understood, which is the reason why more than 30 clinical trials in the past three decades [...] Read more.
Traumatic brain injury (TBI) is a heterogeneous disease in its origin, neuropathology, and prognosis, with no FDA-approved treatments. The pathology of TBI is complicated and not sufficiently understood, which is the reason why more than 30 clinical trials in the past three decades turned out unsuccessful in phase III. The multifaceted pathophysiology of TBI involves a cascade of metabolic and molecular events including inflammation, oxidative stress, excitotoxicity, and mitochondrial dysfunction. In this study, an open head TBI mouse model, induced by controlled cortical impact (CCI), was used to investigate the chronic protective effects of mitoquinone (MitoQ) administration 30 days post-injury. Neurological functions were assessed with the Garcia neuroscore, pole climbing, grip strength, and adhesive removal tests, whereas cognitive and behavioral functions were assessed using the object recognition, Morris water maze, and forced swim tests. As for molecular effects, immunofluorescence staining was conducted to investigate microgliosis, astrocytosis, neuronal cell count, and axonal integrity. The results show that MitoQ enhanced neurological and cognitive functions 30 days post-injury. MitoQ also decreased the activation of astrocytes and microglia, which was accompanied by improved axonal integrity and neuronal cell count in the cortex. Therefore, we conclude that MitoQ has neuroprotective effects in a moderate open head CCI mouse model by decreasing oxidative stress, neuroinflammation, and axonal injury. Full article
(This article belongs to the Special Issue Brain Injury and Neurodegeneration: Molecular, Functional, and Translational Approach)
►▼ Show Figures

Figure 1

27 pages, 48469 KiB  
Article
Transfer RNA-Derived Fragments and isomiRs Are Novel Components of Chronic TBI-Induced Neuropathology
by Noora Puhakka, Shalini Das Gupta, Niina Vuokila and Asla Pitkänen
Biomedicines 2022, 10(1), 136; https://doi.org/10.3390/biomedicines10010136 - 8 Jan 2022
Cited by 9 | Viewed by 2078
Abstract
Neuroinflammation is a secondary injury mechanism that evolves in the brain for months after traumatic brain injury (TBI). We hypothesized that an altered small non-coding RNA (sncRNA) signature plays a key role in modulating post-TBI secondary injury and neuroinflammation. At 3threemonths post-TBI, messenger [...] Read more.
Neuroinflammation is a secondary injury mechanism that evolves in the brain for months after traumatic brain injury (TBI). We hypothesized that an altered small non-coding RNA (sncRNA) signature plays a key role in modulating post-TBI secondary injury and neuroinflammation. At 3threemonths post-TBI, messenger RNA sequencing (seq) and small RNAseq were performed on samples from the ipsilateral thalamus and perilesional cortex of selected rats with a chronic inflammatory endophenotype, and sham-operated controls. The small RNAseq identified dysregulation of 2 and 19 miRNAs in the thalamus and cortex, respectively. The two candidates from the thalamus and the top ten from the cortex were selected for validation. In the thalamus, miR-146a-5p and miR-155-5p levels were upregulated, and in the cortex, miR-375-3p and miR-211-5p levels were upregulated. Analysis of isomiRs of differentially expressed miRNAs identified 3′ nucleotide additions that were increased after TBI. Surprisingly, we found fragments originating from 16 and 13 tRNAs in the thalamus and cortex, respectively. We further analyzed two upregulated fragments, 3′tRF-IleAAT and 3′tRF-LysTTT. Increased expression of the full miR-146a profile, and 3′tRF-IleAAT and 3′tRF-LysTTT was associated with a worse behavioral outcome in animals with chronic neuroinflammation. Our results highlight the importance of understanding the regulatory roles of as-yet unknown sncRNAs for developing better strategies to treat TBI and neuroinflammation. Full article
(This article belongs to the Special Issue Brain Injury and Neurodegeneration: Molecular, Functional, and Translational Approach)
►▼ Show Figures

Figure 1

11 pages, 1031 KiB  
Article
Exosomal microRNA Differential Expression in Plasma of Young Adults with Chronic Mild Traumatic Brain Injury and Healthy Control
by Rany Vorn, Maiko Suarez, Jacob C. White, Carina A. Martin, Hyung-Suk Kim, Chen Lai, Si-Jung Yun, Jessica M. Gill and Hyunhwa Lee
Biomedicines 2022, 10(1), 36; https://doi.org/10.3390/biomedicines10010036 - 24 Dec 2021
Cited by 7 | Viewed by 3578
Abstract
Chronic mild traumatic brain injury (mTBI) has long-term consequences, such as neurological disability, but its pathophysiological mechanism is unknown. Exosomal microRNAs (exomiRNAs) may be important mediators of molecular and cellular changes involved in persistent symptoms after mTBI. We profiled exosomal microRNAs (exomiRNAs) in [...] Read more.
Chronic mild traumatic brain injury (mTBI) has long-term consequences, such as neurological disability, but its pathophysiological mechanism is unknown. Exosomal microRNAs (exomiRNAs) may be important mediators of molecular and cellular changes involved in persistent symptoms after mTBI. We profiled exosomal microRNAs (exomiRNAs) in plasma from young adults with or without a chronic mTBI to decipher the underlying mechanisms of its long-lasting symptoms after mTBI. We identified 25 significantly dysregulated exomiRNAs in the chronic mTBI group (n = 29, with 4.48 mean years since the last injury) compared to controls (n = 11). These miRNAs are associated with pathways of neurological disease, organismal injury and abnormalities, and psychological disease. Dysregulation of these plasma exomiRNAs in chronic mTBI may indicate that neuronal inflammation can last long after the injury and result in enduring and persistent post-injury symptoms. These findings are useful for diagnosing and treating chronic mTBIs. Full article
(This article belongs to the Special Issue Brain Injury and Neurodegeneration: Molecular, Functional, and Translational Approach)
►▼ Show Figures

Figure 1

18 pages, 2386 KiB  
Article
Prophylactic Activation of Shh Signaling Attenuates TBI-Induced Seizures in Zebrafish by Modulating Glutamate Excitotoxicity through Eaat2a
by James Hentig, Leah J. Campbell, Kaylee Cloghessy, Mijoon Lee, William Boggess and David R. Hyde
Biomedicines 2022, 10(1), 32; https://doi.org/10.3390/biomedicines10010032 - 24 Dec 2021
Cited by 5 | Viewed by 2763
Abstract
Approximately 2 million individuals experience a traumatic brain injury (TBI) every year in the United States. Secondary injury begins within minutes after TBI, with alterations in cellular function and chemical signaling that contribute to excitotoxicity. Post-traumatic seizures (PTS) are experienced in an increasing [...] Read more.
Approximately 2 million individuals experience a traumatic brain injury (TBI) every year in the United States. Secondary injury begins within minutes after TBI, with alterations in cellular function and chemical signaling that contribute to excitotoxicity. Post-traumatic seizures (PTS) are experienced in an increasing number of TBI individuals that also display resistance to traditional anti-seizure medications (ASMs). Sonic hedgehog (Shh) is a signaling pathway that is upregulated following central nervous system damage in zebrafish and aids injury-induced regeneration. Using a modified Marmarou weight drop on adult zebrafish, we examined PTS following TBI and Shh modulation. We found that inhibiting Shh signaling by cyclopamine significantly increased PTS in TBI fish, prolonged the timeframe PTS was observed, and decreased survival across all TBI severities. Shh-inhibited TBI fish failed to respond to traditional ASMs, but were attenuated when treated with CNQX, which blocks ionotropic glutamate receptors. We found that the Smoothened agonist, purmorphamine, increased Eaat2a expression in undamaged brains compared to untreated controls, and purmorphamine treatment reduced glutamate excitotoxicity following TBI. Similarly, purmorphamine reduced PTS, edema, and cognitive deficits in TBI fish, while these pathologies were increased and/or prolonged in cyclopamine-treated TBI fish. However, the increased severity of TBI phenotypes with cyclopamine was reduced by cotreating fish with ceftriaxone, which induces Eaat2a expression. Collectively, these data suggest that Shh signaling induces Eaat2a expression and plays a role in regulating TBI-induced glutamate excitotoxicity and TBI sequelae. Full article
(This article belongs to the Special Issue Brain Injury and Neurodegeneration: Molecular, Functional, and Translational Approach)
►▼ Show Figures

Figure 1

13 pages, 3561 KiB  
Article
Bioactive Flavonoids Icaritin and Icariin Protect against Cerebral Ischemia–Reperfusion-Associated Apoptosis and Extracellular Matrix Accumulation in an Ischemic Stroke Mouse Model
by Cheng-Tien Wu, Man-Chih Chen, Shing-Hwa Liu, Ting-Hua Yang, Lin-Hwa Long, Siao-Syun Guan and Chang-Mu Chen
Biomedicines 2021, 9(11), 1719; https://doi.org/10.3390/biomedicines9111719 - 19 Nov 2021
Cited by 15 | Viewed by 2291
Abstract
Stroke, which is the second leading cause of mortality in the world, is urgently needed to explore the medical strategies for ischemic stroke treatment. Both icariin (ICA) and icaritin (ICT) are the major active flavonoids extracted from Herba epimedii that have been regarded [...] Read more.
Stroke, which is the second leading cause of mortality in the world, is urgently needed to explore the medical strategies for ischemic stroke treatment. Both icariin (ICA) and icaritin (ICT) are the major active flavonoids extracted from Herba epimedii that have been regarded as the neuroprotective agents in disease models. In this study, we aimed to investigate and compare the neuroprotective effects of ICA and ICT in a middle cerebral artery occlusion (MCAO) mouse model. Male ICR mice were pretreated with both ICA and ICT, which ameliorated body weight loss, neurological injury, infarct volume, and pathological change in acute ischemic stroke mice. Furthermore, administration of both ICA and ICT could also protect against neuronal cell apoptotic death, oxidative and nitrosative stress, lipid peroxidation, and extracellular matrix (ECM) accumulation in the brains. The neuroprotective effects of ICT are slightly better than that of ICA in acute cerebral ischemic stroke mice. These results suggest that pretreatment with both ICA and ICT improves the neuronal cell apoptosis and responses of oxidative/nitrosative stress and counteracts the ECM accumulation in the brains of acute cerebral ischemic stroke mice. Both ICA and ICT treatment may serve as a useful therapeutic strategy for acute ischemic stroke. Full article
(This article belongs to the Special Issue Brain Injury and Neurodegeneration: Molecular, Functional, and Translational Approach)
►▼ Show Figures

Figure 1

17 pages, 4768 KiB  
Article
Mechanical Stretching-Induced Traumatic Brain Injury Is Mediated by the Formation of GSK-3β-Tau Complex to Impair Insulin Signaling Transduction
by Pei-Wen Cheng, Yi-Chung Wu, Tzyy-Yue Wong, Gwo-Ching Sun and Ching-Jiunn Tseng
Biomedicines 2021, 9(11), 1650; https://doi.org/10.3390/biomedicines9111650 - 9 Nov 2021
Cited by 1 | Viewed by 2883
Abstract
Traumatic brain injury confers a significant and growing public health burden. It is a major environmental risk factor for dementia. Nonetheless, the mechanism by which primary mechanical injury leads to neurodegeneration and an increased risk of dementia-related diseases is unclear. Thus, we aimed [...] Read more.
Traumatic brain injury confers a significant and growing public health burden. It is a major environmental risk factor for dementia. Nonetheless, the mechanism by which primary mechanical injury leads to neurodegeneration and an increased risk of dementia-related diseases is unclear. Thus, we aimed to investigate the effect of stretching on SH-SY5Y neuroblastoma cells that proliferate in vitro. These cells retain the dopamine-β-hydroxylase activity, thus being suitable for neuromechanistic studies. SH-SY5Y cells were cultured on stretchable membranes. The culture conditions contained two groups, namely non-stretched (control) and stretched. They were subjected to cyclic stretching (6 and 24 h) and 25% elongation at 1 Hz. Following stretching at 25% and 1 Hz for 6 h, the mechanical injury changed the mitochondrial membrane potential and triggered oxidative DNA damage at 24 h. Stretching decreased the level of brain-derived neurotrophic factors and increased amyloid-β, thus indicating neuronal stress. Moreover, the mechanical injury downregulated the insulin pathway and upregulated glycogen synthase kinase 3β (GSK-3β)S9/p-Tau protein levels, which caused a neuronal injury. Following 6 and 24 h of stretching, GSK-3βS9 was directly bound to p-TauS396. In contrast, the neuronal injury was improved using GSK-3β inhibitor TWS119, which downregulated amyloid-β/p-Taus396 phosphorylation by enhancing ERK1/2T202/Y204 and AktS473 phosphorylation. Our findings imply that the neurons were under stress and that the inactivation of the GSK3β could alleviate this defect. Full article
(This article belongs to the Special Issue Brain Injury and Neurodegeneration: Molecular, Functional, and Translational Approach)
►▼ Show Figures

Figure 1

25 pages, 114899 KiB  
Article
Chronic Alcoholism and HHV-6 Infection Synergistically Promote Neuroinflammatory Microglial Phenotypes in the Substantia Nigra of the Adult Human Brain
by Nityanand Jain, Marks Smirnovs, Samanta Strojeva, Modra Murovska and Sandra Skuja
Biomedicines 2021, 9(9), 1216; https://doi.org/10.3390/biomedicines9091216 - 14 Sep 2021
Cited by 3 | Viewed by 2944
Abstract
Both chronic alcoholism and human herpesvirus-6 (HHV-6) infection have been identified as promoters of neuroinflammation and known to cause movement-related disorders. Substantia Nigra (SN), the dopaminergic neuron-rich region of the basal ganglia, is involved in regulating motor function and the reward system. Hence, [...] Read more.
Both chronic alcoholism and human herpesvirus-6 (HHV-6) infection have been identified as promoters of neuroinflammation and known to cause movement-related disorders. Substantia Nigra (SN), the dopaminergic neuron-rich region of the basal ganglia, is involved in regulating motor function and the reward system. Hence, we hypothesize the presence of possible synergism between alcoholism and HHV-6 infection in the SN region and report a comprehensive quantification and characterization of microglial functions and morphology in postmortem brain tissue from 44 healthy, age-matched alcoholics and chronic alcoholics. A decrease in the perivascular CD68+ microglia in alcoholics was noted in both the gray and white matter. Additionally, the CD68+/Iba1− microglial subpopulation was found to be the dominant type in the controls. Conversely, in alcoholics, dystrophic changes in microglia were seen with a significant increase in Iba1 expression and perivascular to diffuse migration. An increase in CD11b expression was noted in alcoholics, with the Iba1+/CD11b− subtype promoting inflammation. All the controls were found to be negative for HHV-6 whilst the alcoholics demonstrated HHV-6 positivity in both gray and white matter. Amongst HHV-6 positive alcoholics, all the above-mentioned changes were found to be heightened when compared with HHV-6 negative alcoholics, thereby highlighting the compounding relationship between alcoholism and HHV-6 infection that promotes microglia-mediated neuroinflammation. Full article
(This article belongs to the Special Issue Brain Injury and Neurodegeneration: Molecular, Functional, and Translational Approach)
►▼ Show Figures

Figure 1

19 pages, 3398 KiB  
Article
Fatty Acid-Binding Proteins Aggravate Cerebral Ischemia-Reperfusion Injury in Mice
by Qingyun Guo, Ichiro Kawahata, Tomohide Degawa, Yuri Ikeda-Matsuo, Meiling Sun, Feng Han and Kohji Fukunaga
Biomedicines 2021, 9(5), 529; https://doi.org/10.3390/biomedicines9050529 - 10 May 2021
Cited by 15 | Viewed by 3169
Abstract
Fatty acid-binding proteins (FABPs) regulate the intracellular dynamics of fatty acids, mediate lipid metabolism and participate in signaling processes. However, the therapeutic efficacy of targeting FABPs as novel therapeutic targets for cerebral ischemia is not well established. Previously, we synthesized a novel FABP [...] Read more.
Fatty acid-binding proteins (FABPs) regulate the intracellular dynamics of fatty acids, mediate lipid metabolism and participate in signaling processes. However, the therapeutic efficacy of targeting FABPs as novel therapeutic targets for cerebral ischemia is not well established. Previously, we synthesized a novel FABP inhibitor, i.e., FABP ligand 6 [4-(2-(5-(2-chlorophenyl)-1-(4-isopropylphenyl)-1H-pyrazol-3-yl)-4-fluorophenoxy)butanoic acid] (referred to here as MF6). In this study, we analyzed the ability of MF6 to ameliorate transient middle cerebral artery occlusion (tMCAO) and reperfusion-induced injury in mice. A single MF6 administration (3.0 mg/kg, per os) at 0.5 h post-reperfusion effectively reduced brain infarct volumes and neurological deficits. The protein-expression levels of FABP3, FABP5 and FABP7 in the brain gradually increased after tMCAO. Importantly, MF6 significantly suppressed infarct volumes and the elevation of FABP-expression levels at 12 h post-reperfusion. MF6 also inhibited the promotor activity of FABP5 in human neuroblastoma cells (SH-SY5Y). These data suggest that FABPs elevated infarct volumes after ischemic stroke and that inhibiting FABPs ameliorated the ischemic injury. Moreover, MF6 suppressed the inflammation-associated prostaglandin E2 levels through microsomal prostaglandin E synthase-1 expression in the ischemic hemispheres. Taken together, the results imply that the FABP inhibitor MF6 can potentially serve as a neuroprotective therapeutic for ischemic stroke. Full article
(This article belongs to the Special Issue Brain Injury and Neurodegeneration: Molecular, Functional, and Translational Approach)
►▼ Show Figures

Figure 1

11 pages, 1096 KiB  
Article
Brain Metabolic Correlates of Persistent Olfactory Dysfunction after SARS-Cov2 Infection
by Maria Isabella Donegani, Alberto Miceli, Matteo Pardini, Matteo Bauckneht, Silvia Chiola, Michele Pennone, Cecilia Marini, Federico Massa, Stefano Raffa, Giulia Ferrarazzo, Dario Arnaldi, Gianmario Sambuceti, Flavio Nobili and Silvia Morbelli
Biomedicines 2021, 9(3), 287; https://doi.org/10.3390/biomedicines9030287 - 12 Mar 2021
Cited by 35 | Viewed by 3834
Abstract
We aimed to evaluate the brain hypometabolic signature of persistent isolated olfactory dysfunction after SARS-CoV-2 infection. Twenty-two patients underwent whole-body [18F]-FDG PET, including a dedicated brain acquisition at our institution between May and December 2020 following their recovery after SARS-Cov2 infection. [...] Read more.
We aimed to evaluate the brain hypometabolic signature of persistent isolated olfactory dysfunction after SARS-CoV-2 infection. Twenty-two patients underwent whole-body [18F]-FDG PET, including a dedicated brain acquisition at our institution between May and December 2020 following their recovery after SARS-Cov2 infection. Fourteen of these patients presented isolated persistent hyposmia (smell diskettes olfaction test was used). A voxel-wise analysis (using Statistical Parametric Mapping software version 8 (SPM8)) was performed to identify brain regions of relative hypometabolism in patients with hyposmia with respect to controls. Structural connectivity of these regions was assessed (BCB toolkit). Relative hypometabolism was demonstrated in bilateral parahippocampal and fusiform gyri and in left insula in patients with respect to controls. Structural connectivity maps highlighted the involvement of bilateral longitudinal fasciculi. This study provides evidence of cortical hypometabolism in patients with isolated persistent hyposmia after SARS-Cov2 infection. [18F]-FDG PET may play a role in the identification of long-term brain functional sequelae of COVID-19. Full article
(This article belongs to the Special Issue Brain Injury and Neurodegeneration: Molecular, Functional, and Translational Approach)
►▼ Show Figures

Figure 1

Review

Jump to: Editorial, Research, Other

20 pages, 1503 KiB  
Review
Histone Deacetylases and Their Isoform-Specific Inhibitors in Ischemic Stroke
by Svetlana Demyanenko, Valentina Dzreyan and Svetlana Sharifulina
Biomedicines 2021, 9(10), 1445; https://doi.org/10.3390/biomedicines9101445 - 11 Oct 2021
Cited by 12 | Viewed by 2487
Abstract
Cerebral ischemia is the second leading cause of death in the world and multimodal stroke therapy is needed. The ischemic stroke generally reduces the gene expression due to suppression of acetylation of histones H3 and H4. Histone deacetylases inhibitors have been shown to [...] Read more.
Cerebral ischemia is the second leading cause of death in the world and multimodal stroke therapy is needed. The ischemic stroke generally reduces the gene expression due to suppression of acetylation of histones H3 and H4. Histone deacetylases inhibitors have been shown to be effective in protecting the brain from ischemic damage. Histone deacetylases inhibitors induce neurogenesis and angiogenesis in damaged brain areas promoting functional recovery after cerebral ischemia. However, the role of different histone deacetylases isoforms in the survival and death of brain cells after stroke is still controversial. This review aims to analyze the data on the neuroprotective activity of nonspecific and selective histone deacetylase inhibitors in ischemic stroke. Full article
(This article belongs to the Special Issue Brain Injury and Neurodegeneration: Molecular, Functional, and Translational Approach)
►▼ Show Figures

Figure 1

25 pages, 2583 KiB  
Review
The Childhood-Onset Neurodegeneration with Cerebellar Atrophy (CONDCA) Disease Caused by AGTPBP1 Gene Mutations: The Purkinje Cell Degeneration Mouse as an Animal Model for the Study of this Human Disease
by Fernando C. Baltanás, María T. Berciano, Eugenio Santos and Miguel Lafarga
Biomedicines 2021, 9(9), 1157; https://doi.org/10.3390/biomedicines9091157 - 4 Sep 2021
Cited by 11 | Viewed by 3011
Abstract
Recent reports have identified rare, biallelic damaging variants of the AGTPBP1 gene that cause a novel and documented human disease known as childhood-onset neurodegeneration with cerebellar atrophy (CONDCA), linking loss of function of the AGTPBP1 protein to human neurodegenerative diseases. CONDCA patients exhibit [...] Read more.
Recent reports have identified rare, biallelic damaging variants of the AGTPBP1 gene that cause a novel and documented human disease known as childhood-onset neurodegeneration with cerebellar atrophy (CONDCA), linking loss of function of the AGTPBP1 protein to human neurodegenerative diseases. CONDCA patients exhibit progressive cognitive decline, ataxia, hypotonia or muscle weakness among other clinical features that may be fatal. Loss of AGTPBP1 in humans recapitulates the neurodegenerative course reported in a well-characterised murine animal model harbouring loss-of-function mutations in the AGTPBP1 gene. In particular, in the Purkinje cell degeneration (pcd) mouse model, mutations in AGTPBP1 lead to early cerebellar ataxia, which correlates with the massive loss of cerebellar Purkinje cells. In addition, neurodegeneration in the olfactory bulb, retina, thalamus and spinal cord were also reported. In addition to neurodegeneration, pcd mice show behavioural deficits such as cognitive decline. Here, we provide an overview of what is currently known about the structure and functional role of AGTPBP1 and discuss the various alterations in AGTPBP1 that cause neurodegeneration in the pcd mutant mouse and humans with CONDCA. The sequence of neuropathological events that occur in pcd mice and the mechanisms governing these neurodegenerative processes are also reported. Finally, we describe the therapeutic strategies that were applied in pcd mice and focus on the potential usefulness of pcd mice as a promising model for the development of new therapeutic strategies for clinical trials in humans, which may offer potential beneficial options for patients with AGTPBP1 mutation-related CONDCA. Full article
(This article belongs to the Special Issue Brain Injury and Neurodegeneration: Molecular, Functional, and Translational Approach)
►▼ Show Figures

Graphical abstract

45 pages, 24138 KiB  
Review
Alzheimer’s Disease: A Molecular View of β-Amyloid Induced Morbific Events
by Rajmohamed Mohamed Asik, Natarajan Suganthy, Mohamed Asik Aarifa, Arvind Kumar, Krisztián Szigeti, Domokos Mathe, Balázs Gulyás, Govindaraju Archunan and Parasuraman Padmanabhan
Biomedicines 2021, 9(9), 1126; https://doi.org/10.3390/biomedicines9091126 - 1 Sep 2021
Cited by 23 | Viewed by 5152
Abstract
Amyloid-β (Aβ) is a dynamic peptide of Alzheimer’s disease (AD) which accelerates the disease progression. At the cell membrane and cell compartments, the amyloid precursor protein (APP) undergoes amyloidogenic cleavage by β- and γ-secretases and engenders the Aβ. In addition, externally produced Aβ [...] Read more.
Amyloid-β (Aβ) is a dynamic peptide of Alzheimer’s disease (AD) which accelerates the disease progression. At the cell membrane and cell compartments, the amyloid precursor protein (APP) undergoes amyloidogenic cleavage by β- and γ-secretases and engenders the Aβ. In addition, externally produced Aβ gets inside the cells by receptors mediated internalization. An elevated amount of Aβ yields spontaneous aggregation which causes organelles impairment. Aβ stimulates the hyperphosphorylation of tau protein via acceleration by several kinases. Aβ travels to the mitochondria and interacts with its functional complexes, which impairs the mitochondrial function leading to the activation of apoptotic signaling cascade. Aβ disrupts the Ca2+ and protein homeostasis of the endoplasmic reticulum (ER) and Golgi complex (GC) that promotes the organelle stress and inhibits its stress recovery machinery such as unfolded protein response (UPR) and ER-associated degradation (ERAD). At lysosome, Aβ precedes autophagy dysfunction upon interacting with autophagy molecules. Interestingly, Aβ act as a transcription regulator as well as inhibits telomerase activity. Both Aβ and p-tau interaction with neuronal and glial receptors elevate the inflammatory molecules and persuade inflammation. Here, we have expounded the Aβ mediated events in the cells and its cosmopolitan role on neurodegeneration, and the current clinical status of anti-amyloid therapy. Full article
(This article belongs to the Special Issue Brain Injury and Neurodegeneration: Molecular, Functional, and Translational Approach)
►▼ Show Figures

Figure 1

14 pages, 508 KiB  
Review
Pharmacological and Therapeutic Approaches in the Treatment of Epilepsy
by Shampa Ghosh, Jitendra Kumar Sinha, Tarab Khan, Kuramkote Shivanna Devaraju, Prabhakar Singh, Kumar Vaibhav and Pankaj Gaur
Biomedicines 2021, 9(5), 470; https://doi.org/10.3390/biomedicines9050470 - 25 Apr 2021
Cited by 31 | Viewed by 8243
Abstract
Epilepsy affects around 50 million people across the globe and is the third most common chronic brain disorder. It is a non-communicable disease of the brain that affects people of all ages. It is accompanied by depression, anxiety, and substantially increased morbidity and [...] Read more.
Epilepsy affects around 50 million people across the globe and is the third most common chronic brain disorder. It is a non-communicable disease of the brain that affects people of all ages. It is accompanied by depression, anxiety, and substantially increased morbidity and mortality. A large number of third-generation anti-epileptic drugs are available, but they have multiple side-effects causing a decline in the quality of life. The inheritance and etiology of epilepsy are complex with multiple underlying genetic and epigenetic mechanisms. Different neurotransmitters play intricate functions to maintain the normal physiology of various neurons. If there is any dysregulation of neurotransmission due to aberrant transmitter levels or their receptor biology, it can result in seizures. In this review, we have discussed the roles played by various neurotransmitters and their receptors in the pathophysiology of epilepsy. Drug-resistant epilepsy (DRE) has remained one of the forefront areas of epilepsy research for a long time. Understanding the mechanisms underlying DRE is of utmost importance because of its high incidence rate among epilepsy patients and increased risks of psychosocial problems and premature death. Here we have enumerated various hypotheses of DRE. Further, we have discussed different non-conventional therapeutic strategies, including combination therapy and non-drug treatment. The recent studies supporting the modern approaches for the treatment of epilepsy have been deliberated with particular reference to the mTOR pathway, breakdown of the blood-brain barrier, and inflammatory pathways. Full article
(This article belongs to the Special Issue Brain Injury and Neurodegeneration: Molecular, Functional, and Translational Approach)
►▼ Show Figures

Figure 1

42 pages, 1306 KiB  
Review
Revisiting Traumatic Brain Injury: From Molecular Mechanisms to Therapeutic Interventions
by Abbas Jarrahi, Molly Braun, Meenakshi Ahluwalia, Rohan V. Gupta, Michael Wilson, Stephanie Munie, Pankaj Ahluwalia, John R. Vender, Fernando L. Vale, Krishnan M. Dhandapani and Kumar Vaibhav
Biomedicines 2020, 8(10), 389; https://doi.org/10.3390/biomedicines8100389 - 29 Sep 2020
Cited by 93 | Viewed by 16160
Abstract
Studying the complex molecular mechanisms involved in traumatic brain injury (TBI) is crucial for developing new therapies for TBI. Current treatments for TBI are primarily focused on patient stabilization and symptom mitigation. However, the field lacks defined therapies to prevent cell death, oxidative [...] Read more.
Studying the complex molecular mechanisms involved in traumatic brain injury (TBI) is crucial for developing new therapies for TBI. Current treatments for TBI are primarily focused on patient stabilization and symptom mitigation. However, the field lacks defined therapies to prevent cell death, oxidative stress, and inflammatory cascades which lead to chronic pathology. Little can be done to treat the mechanical damage that occurs during the primary insult of a TBI; however, secondary injury mechanisms, such as inflammation, blood-brain barrier (BBB) breakdown, edema formation, excitotoxicity, oxidative stress, and cell death, can be targeted by therapeutic interventions. Elucidating the many mechanisms underlying secondary injury and studying targets of neuroprotective therapeutic agents is critical for developing new treatments. Therefore, we present a review on the molecular events following TBI from inflammation to programmed cell death and discuss current research and the latest therapeutic strategies to help understand TBI-mediated secondary injury. Full article
(This article belongs to the Special Issue Brain Injury and Neurodegeneration: Molecular, Functional, and Translational Approach)
►▼ Show Figures

Graphical abstract

37 pages, 2948 KiB  
Review
Neuroprotection: Targeting Multiple Pathways by Naturally Occurring Phytochemicals
by Andleeb Khan, Sadaf Jahan, Zuha Imtiyaz, Saeed Alshahrani, Hafiz Antar Makeen, Bader Mohammed Alshehri, Ajay Kumar, Azher Arafah and Muneeb U. Rehman
Biomedicines 2020, 8(8), 284; https://doi.org/10.3390/biomedicines8080284 - 12 Aug 2020
Cited by 44 | Viewed by 7549
Abstract
With the increase in the expectancy of the life span of humans, neurodegenerative diseases (NDs) have imposed a considerable burden on the family, society, and nation. In defiance of the breakthroughs in the knowledge of the pathogenesis and underlying mechanisms of various NDs, [...] Read more.
With the increase in the expectancy of the life span of humans, neurodegenerative diseases (NDs) have imposed a considerable burden on the family, society, and nation. In defiance of the breakthroughs in the knowledge of the pathogenesis and underlying mechanisms of various NDs, very little success has been achieved in developing effective therapies. This review draws a bead on the availability of the nutraceuticals to date for various NDs (Alzheimer’s disease, Parkinson’s disease, Amyotrophic lateral sclerosis, Huntington’s disease, vascular cognitive impairment, Prion disease, Spinocerebellar ataxia, Spinal muscular atrophy, Frontotemporal dementia, and Pick’s disease) focusing on their various mechanisms of action in various in vivo and in vitro models of NDs. This review is distinctive in its compilation to critically review preclinical and clinical studies of the maximum phytochemicals in amelioration and prevention of almost all kinds of neurodegenerative diseases and address their possible mechanism of action. PubMed, Embase, and Cochrane Library searches were used for preclinical studies, while ClinicalTrials.gov and PubMed were searched for clinical updates. The results from preclinical studies demonstrate the efficacious effects of the phytochemicals in various NDs while clinical reports showing mixed results with promise for phytochemical use as an adjunct to the conventional treatment in various NDs. These studies together suggest that phytochemicals can significantly act upon different mechanisms of disease such as oxidative stress, inflammation, apoptotic pathways, and gene regulation. However, further clinical studies are needed that should include the appropriate biomarkers of NDs and the effect of phytochemicals on them as well as targeting the appropriate population. Full article
(This article belongs to the Special Issue Brain Injury and Neurodegeneration: Molecular, Functional, and Translational Approach)
►▼ Show Figures

Graphical abstract

Other

19 pages, 2338 KiB  
Systematic Review
Considerations about Hypoxic Changes in Neuraxis Tissue Injuries and Recovery
by Simona Isabelle Stoica, Coralia Bleotu, Vlad Ciobanu, Anca Mirela Ionescu, Irina Albadi, Gelu Onose and Constantin Munteanu
Biomedicines 2022, 10(2), 481; https://doi.org/10.3390/biomedicines10020481 - 18 Feb 2022
Cited by 17 | Viewed by 2697
Abstract
Hypoxia represents the temporary or longer-term decrease or deprivation of oxygen in organs, tissues, and cells after oxygen supply drops or its excessive consumption. Hypoxia can be (para)-physiological—adaptive—or pathological. Thereby, the mechanisms of hypoxia have many implications, such as in adaptive processes of [...] Read more.
Hypoxia represents the temporary or longer-term decrease or deprivation of oxygen in organs, tissues, and cells after oxygen supply drops or its excessive consumption. Hypoxia can be (para)-physiological—adaptive—or pathological. Thereby, the mechanisms of hypoxia have many implications, such as in adaptive processes of normal cells, but to the survival of neoplastic ones, too. Ischemia differs from hypoxia as it means a transient or permanent interruption or reduction of the blood supply in a given region or tissue and consequently a poor provision with oxygen and energetic substratum-inflammation and oxidative stress damages generating factors. Considering the implications of hypoxia on nerve tissue cells that go through different ischemic processes, in this paper, we will detail the molecular mechanisms by which such structures feel and adapt to hypoxia. We will present the hypoxic mechanisms and changes in the CNS. Also, we aimed to evaluate acute, subacute, and chronic central nervous hypoxic-ischemic changes, hoping to understand better and systematize some neuro-muscular recovery methods necessary to regain individual independence. To establish the link between CNS hypoxia, ischemic-lesional mechanisms, and neuro-motor and related recovery, we performed a systematic literature review following the” Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA”) filtering method by interrogating five international medical renown databases, using, contextually, specific keywords combinations/”syntaxes”, with supplementation of the afferent documentation through an amount of freely discovered, also contributive, bibliographic resources. As a result, 45 papers were eligible according to the PRISMA-inspired selection approach, thus covering information on both: intimate/molecular path-physiological specific mechanisms and, respectively, consequent clinical conditions. Such a systematic process is meant to help us construct an article structure skeleton giving a primary objective input about the assembly of the literature background to be approached, summarised, and synthesized. The afferent contextual search (by keywords combination/syntaxes) we have fulfilled considerably reduced the number of obtained articles. We consider this systematic literature review is warranted as hypoxia’s mechanisms have opened new perspectives for understanding ischemic changes in the CNS neuraxis tissue/cells, starting at the intracellular level and continuing with experimental research to recover the consequent clinical-functional deficits better. Full article
(This article belongs to the Special Issue Brain Injury and Neurodegeneration: Molecular, Functional, and Translational Approach)
►▼ Show Figures

Figure 1

18 pages, 1124 KiB  
Systematic Review
Effects of Treadmill Exercise on Neural Mitochondrial Functions in Parkinson’s Disease: A Systematic Review of Animal Studies
by Nguyen Thanh Nhu, Yu-Jung Cheng and Shin-Da Lee
Biomedicines 2021, 9(8), 1011; https://doi.org/10.3390/biomedicines9081011 - 13 Aug 2021
Cited by 9 | Viewed by 2650
Abstract
This systematic review sought to determine the effects of treadmill exercise on the neural mitochondrial respiratory deficiency and neural mitochondrial quality-control dysregulation in Parkinson’s disease. PubMed, Web of Science, and EMBASE databases were searched through March 2020. The English-published animal studies that mentioned [...] Read more.
This systematic review sought to determine the effects of treadmill exercise on the neural mitochondrial respiratory deficiency and neural mitochondrial quality-control dysregulation in Parkinson’s disease. PubMed, Web of Science, and EMBASE databases were searched through March 2020. The English-published animal studies that mentioned the effects of treadmill exercise on neural mitochondria in Parkinson’s disease were included. The CAMARADES checklist was used to assess the methodological quality of the studies. Ten controlled trials were included (median CAMARADES score = 5.7/10) with various treadmill exercise durations (1–18 weeks). Seven studies analyzed the neural mitochondrial respiration, showing that treadmill training attenuated complex I deficits, cytochrome c release, ATP depletion, and complexes II–V abnormalities in Parkinson’s disease. Nine studies analyzed the neural mitochondrial quality-control, reporting that treadmill exercise improved mitochondrial biogenesis, mitochondrial fusion, and mitophagy in Parkinson’s disease. The review findings supported the hypothesis that treadmill training could attenuate both neural mitochondrial respiratory deficiency and neural mitochondrial quality-control dysregulation in Parkinson’s disease, suggesting that treadmill training might slow down the progression of Parkinson’s disease. Full article
(This article belongs to the Special Issue Brain Injury and Neurodegeneration: Molecular, Functional, and Translational Approach)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-19
Back to TopTop