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Keywords = post-stroke cognitive impairment

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41 pages, 40949 KiB  
Article
Neurobiomechanical Characterization of Feedforward Phase of Gait Initiation in Chronic Stroke: A Linear and Non-Linear Approach
by Marta Freitas, Pedro Fonseca, Leonel Alves, Liliana Pinho, Sandra Silva, Vânia Figueira, José Félix, Francisco Pinho, João Paulo Vilas-Boas and Augusta Silva
Appl. Sci. 2025, 15(9), 4762; https://doi.org/10.3390/app15094762 - 25 Apr 2025
Viewed by 115
Abstract
Postural control arises from the complex interplay of stability, adaptability, and dynamic adjustments, which are disrupted post-stroke, emphasizing the importance of examining these mechanisms during functional tasks. This study aimed to analyze the complexity and variability of postural control in post-stroke individuals during [...] Read more.
Postural control arises from the complex interplay of stability, adaptability, and dynamic adjustments, which are disrupted post-stroke, emphasizing the importance of examining these mechanisms during functional tasks. This study aimed to analyze the complexity and variability of postural control in post-stroke individuals during the feedforward phase of gait initiation. A cross-sectional study analyzed 17 post-stroke individuals and 16 matched controls. Participants had a unilateral ischemic stroke in the chronic phase and could walk independently. Exclusions included cognitive impairments, recent surgery, and neurological/orthopedic conditions. Kinematic and kinetic data were collected during 10 self-initiated gait trials to analyze centre of pressure (CoP) dynamics and joint angles (−600 ms to +50 ms). A 12-camera motion capture system (Qualisys, Gothenburg, Sweden) recorded full-body kinematics using 72 reflective markers placed on anatomical landmarks of the lower limbs, pelvis, trunk, and upper limbs. Ground reaction forces were measured via force plates (Bertec, Columbus, OH, USA) to compute CoP variables. Linear (displacement, amplitude, and velocity) and non-linear (Lyapunov exponent—LyE and multiscale entropy—MSE) measures were applied to assess postural control complexity and variability. Mann–Whitney U tests were applied (p < 0.05). The stroke group showed greater CoP displacement (p < 0.05) and reduced velocity (p = 0.021). Non-linear analysis indicated lower LyE values and reduced complexity and adaptability in CoP position and amplitude across scales (p < 0.05). In the sagittal plane, the stroke group had higher displacement and amplitude in the head, trunk, pelvis, and limbs, with reduced LyE and MSE values (p < 0.05). Frontal plane findings showed increased displacement and amplitude in the head, trunk, and ankle, with reduced LyE and MSE (p < 0.05). In the transverse plane, exaggerated rotational patterns were observed with increased displacement and amplitude in the head, trunk, pelvis, and hip, alongside reduced LyE convergence and MSE complexity (p < 0.05). Stroke survivors exhibit increased linear variability, indicating instability, and reduced non-linear complexity, reflecting limited adaptability. These results highlight the need for rehabilitation strategies that address both stability and adaptability across time scales. Full article
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16 pages, 36996 KiB  
Article
AMX0035 Mitigates Oligodendrocyte Apoptosis and Ameliorates Demyelination in MCAO Rats by Inhibiting Endoplasmic Reticulum Stress and Mitochondrial Dysfunction
by Li Zhang, Cunhao Bian, Yusen Wang, Ling Wei, Shanquan Sun and Qian Liu
Int. J. Mol. Sci. 2025, 26(8), 3865; https://doi.org/10.3390/ijms26083865 - 19 Apr 2025
Viewed by 307
Abstract
Post-stroke cognitive impairment (PSCI) is a common complication of strokes and is associated with the demyelination of nerve fibers. AMX0035, a drug currently used to treat motor neuron diseases, may aid in preventing oligodendrocyte apoptosis and alleviating demyelination by targeting the pathways involved [...] Read more.
Post-stroke cognitive impairment (PSCI) is a common complication of strokes and is associated with the demyelination of nerve fibers. AMX0035, a drug currently used to treat motor neuron diseases, may aid in preventing oligodendrocyte apoptosis and alleviating demyelination by targeting the pathways involved in ERS and mitochondrial dysfunction. All animals were randomly divided into four groups: the sham, sham+AMX0035, middle cerebral artery occlusion (MCAO), and MCAO+AMX0035 group. The Morris water maze was used to test cognitive function, and changes in myelin structure in the brain were investigated using transmission electron microscopy (TEM), Luxol fast blue (LFB) staining, and myelin basic protein (MBP) immunofluorescence staining. Western blot was performed to detect proteins associated with ER stress and mitochondrial dysfunction, and double-labeling immunofluorescence was utilized to localize oligodendrocytes and apoptosis-related proteins. Neurological function scores and TTC staining confirmed the successful establishment of the MCAO rat model. The Morris water maze experiment revealed impaired cognitive function in MCAO rats, which significantly improved following the AMX0035 intervention. TEM and LFB staining showed the disrupted myelin structure in the MCAO group, while AMX0035 effectively ameliorated this myelin damage. Immunofluorescence examination and Western blot revealed the decreased expression of MBP in MCAO rats, increasing with AMX0035 treatment. TUNEL staining demonstrated increased cell apoptosis in MCAO rats, which was reduced following AMX0035 therapy. Western blot detected significant increases in proteins associated with the ER stress pathway and proteins linked to mitochondrial dysfunction in the MCAO group, all of which were downregulated after AMX0035 intervention. Double-labeling immunofluorescence staining revealed a significant increase in the number of cytochrome c+ and caspase 12+ oligodendrocyte cells in MCAO rats, which decreased after AMX0035 administration. The activation of ER stress and mitochondrial dysfunction pathways following MCAO led to oligodendrocyte damage and apoptosis. AMX0035 can inhibit these pathways, reduce oligodendrocyte apoptosis, and alleviate demyelination, thereby improving PSCI. Full article
(This article belongs to the Section Molecular Neurobiology)
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14 pages, 885 KiB  
Article
Non-Verbal Working Memory in Post-Stroke Motor Aphasia: A Pilot Study Using the Tactual Span
by Eyal Heled, Ohad Levi, Elana Strobinsky and Gabi Zeilig
Neurol. Int. 2025, 17(4), 58; https://doi.org/10.3390/neurolint17040058 - 17 Apr 2025
Viewed by 225
Abstract
Background: Working memory (WM) impairment is a potential consequence of motor aphasia resulting from left-hemisphere ischemic stroke. While verbal WM has been studied extensively in this disorder, research regarding non-verbal modalities remains limited, particularly visuospatial WM, tactile WM, and the relationship between [...] Read more.
Background: Working memory (WM) impairment is a potential consequence of motor aphasia resulting from left-hemisphere ischemic stroke. While verbal WM has been studied extensively in this disorder, research regarding non-verbal modalities remains limited, particularly visuospatial WM, tactile WM, and the relationship between them. Additionally, language impairments limit the ability to assess WM in aphasia patients, highlighting the necessity of non-verbal diagnostic tools in clinical practice. The current study’s objectives were to compare tactile and visuospatial WM in patients with post-stroke motor aphasia and to validate the one-hand version of the Tactual Span task as a clinical measure of WM. Methods: A total of 29 participants—14 with post-stroke motor aphasia and 15 healthy controls—completed a battery of cognitive tests, including the Raven’s Colored Progressive Matrices Test, the Visuospatial Span, the Tactual Span, and a visual 1-Back task. Results: There was significantly lower performance across all WM tasks in the aphasia group compared to the controls. Additionally, the Tactual Span successfully discriminated between patients and controls, showing sensitivity estimates of 92.9% and a specificity of 66.7%, with a cut-off score of 4.5 (AUC = 0.91), for the forward stage. The backward stage revealed a sensitivity of 71.4% and a specificity of 73.3%, with a cut-off score of 3.5 (AUC = 0.83). Conclusions: The findings may suggest that non-verbal WM impairment in post-stroke aphasia affects both visuospatial and tactile modalities similarly. Furthermore, the Tactual Span appears to be sensitive to left-hemisphere stroke damage, suggesting its potential utility as a clinical tool for WM assessment in patients with motor aphasia. Full article
(This article belongs to the Special Issue Cognitive Impairment After Stroke)
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28 pages, 1317 KiB  
Article
Effects of Mindfulness and Exercise on Growth Factors, Inflammation, and Stress Markers in Chronic Stroke: The MindFit Project Randomized Clinical Trial
by Adrià Bermudo-Gallaguet, Mar Ariza, Daniela Agudelo, Neus Camins-Vila, Maria Boldó, Sarah Peters, Angelika Katarzyna Sawicka, Rosalia Dacosta-Aguayo, Juan José Soriano-Raya, Marc Via, Imma C. Clemente, Alberto García-Molina, Maria José Durà Mata, Pere Torán-Monserrat, Kirk I. Erickson and Maria Mataró
J. Clin. Med. 2025, 14(8), 2580; https://doi.org/10.3390/jcm14082580 - 9 Apr 2025
Viewed by 627
Abstract
Background/Objectives: Stroke often leads to persistent cognitive and emotional impairments, which rehabilitation may mitigate. However, the biological mechanisms underlying such improvements remain unclear. This study investigated whether supplementing computerized cognitive training (CCT) with mindfulness-based stress reduction (MBSR) or physical exercise (PE) modulated [...] Read more.
Background/Objectives: Stroke often leads to persistent cognitive and emotional impairments, which rehabilitation may mitigate. However, the biological mechanisms underlying such improvements remain unclear. This study investigated whether supplementing computerized cognitive training (CCT) with mindfulness-based stress reduction (MBSR) or physical exercise (PE) modulated biomarkers of neuroplasticity, inflammation, and stress in patients with chronic stroke compared to CCT alone. We also explored whether biomarker changes mediated or correlated with behavioral improvements. Methods: In a three-arm, single-blind, randomized controlled trial (NCT04759950), 141 patients with chronic stroke were randomized (1:1:1) to MBSR+CCT, PE+CCT, or CCT-only for 12 weeks. Plasma levels of brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), vascular endothelial growth factor (VEGF), C-reactive protein (CRP), interleukin-6 (IL-6), and cortisol were measured at baseline and post-intervention. Cognitive, mental health, mindfulness, and fitness outcomes were also assessed. Between- and within-group changes were analyzed using ANCOVA and paired t-tests. Per-protocol and complete-case analyses were conducted. Results: Among the 109 participants with ≥80% adherence, the only significant between-group difference was for VEGF: it remained stable in the MBSR+CCT group but declined in PE+CCT and CCT-only. Within-group analyses showed significant decreases in cortisol in MBSR+CCT and PE+CCT, while IGF-1 levels declined across all groups. In contrast, BDNF, IL-6, and CRP did not show significant changes, and biomarker changes were not significantly associated with behavioral improvements. Complete-case analysis (n = 126) yielded similar findings. Conclusions: Our findings suggest that combining MBSR or PE with CCT may modulate certain biological processes relevant to stroke recovery. MBSR may help maintain VEGF levels, which could support vascular health, while MBSR and PE may contribute to lowering cortisol levels. However, since no clear association with behavioral improvements was found, further research is needed to determine the clinical relevance of these biomarker changes in stroke recovery. Full article
(This article belongs to the Section Mental Health)
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13 pages, 1328 KiB  
Review
Remotely Supervised Transcranial Direct Current Stimulation in Post-Stroke Recovery: A Scoping Review
by Melike Kocahasan, Melissa D. Stockbridge, Joan Stilling, Rene L. Utianski, Rajani Sebastian and Zafer Keser
Medicina 2025, 61(4), 627; https://doi.org/10.3390/medicina61040627 - 29 Mar 2025
Viewed by 340
Abstract
Background and Objectives: Stroke is a leading cause of disability worldwide. Recent studies have suggested the feasibility and potential utility of remotely supervised transcranial direct current stimulation (RS-tDCS) to improve different types of impairments in various neurological conditions. This scoping review provides [...] Read more.
Background and Objectives: Stroke is a leading cause of disability worldwide. Recent studies have suggested the feasibility and potential utility of remotely supervised transcranial direct current stimulation (RS-tDCS) to improve different types of impairments in various neurological conditions. This scoping review provides a critical appraisal of RS-tDCS as an adjunct therapy to enhance recovery after stroke. Materials and Methods: A comprehensive literature review was systematically conducted using PubMed through Nested Knowledge software. A supplementary search was conducted in Google Scholar. Two independent authors screened and identified related studies investigating RS-tDCS in patients with stroke from inception to February 2025. Results: Studies showed that RS-tDCS was safe, with only mild side effects. Additionally, it was feasible, with high adherence rates likely due to ease of use. Regarding efficacy, RS-tDCS preliminarily yielded improvements in upper- and lower-limb motor functions and increased language and cognitive performance. However, the studies were underpowered and heterogeneous, limiting generalization of findings. Conclusions: RS-tDCS is safe and feasible, affording beneficial effects in the motor, language, and cognitive functions of patients with post-stroke impairments. RS-tDCS has the potential to improve access and reduce disparities for post-stroke experimental treatments. However, adequately powered randomized trials are needed to further investigate the efficacy. Full article
(This article belongs to the Section Neurology)
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13 pages, 579 KiB  
Review
The Role of Near-Infrared Spectroscopy (NIRS) in Neurological and Neurodegenerative Diseases as Support to Clinical Practice: An Overview of the Literature
by Elvira Gjonaj, Caterina Formica, Emanuele Cartella, Nunzio Muscarà, Silvia Marino, Angelo Quartarone and Simona De Salvo
Diagnostics 2025, 15(7), 869; https://doi.org/10.3390/diagnostics15070869 - 28 Mar 2025
Viewed by 431
Abstract
Near-Infrared Spectroscopy (NIRS) is a non-invasive technique that measures the oxygenation variations of brain tissue in response to different stimuli. It has many advantages such as being easy to use, portable, and non-invasive. Several studies over the years have demonstrated the usefulness of [...] Read more.
Near-Infrared Spectroscopy (NIRS) is a non-invasive technique that measures the oxygenation variations of brain tissue in response to different stimuli. It has many advantages such as being easy to use, portable, and non-invasive. Several studies over the years have demonstrated the usefulness of NIRS in neurological and neurodegenerative diseases. NIRS remains relatively underutilized in clinical practice. The aim of this brief review was to describe the use of NIRS in neurological and neurodegenerative diseases and how its use can modify clinical, therapeutic, and rehabilitative approaches. A total of 54 relevant articles were selected from the PUBMED research database related to the diagnostic and prognostic role of fNIRS in the main neurological and neurodegenerative diseases; significant outcomes have been reported in a descriptive form with careful considerations. In addition, we excluded studies using fNIRS in co-registration with other neurophysiological techniques. The use of NIRS should be applied even in the field of neurological and neurodegenerative diseases; in dementia, NIRS can aid in differential diagnosis and predict possible evolutions from Mild Cognitive Impairment (MCI) to Alzheimer’s Disease (AD) stage; in stroke, it plays an important role especially in the post-acute phase, giving information about the patient’s chances of recovery; in Parkinson’s Disease (PD), the results showed the important role of cognitive aspects; in epilepsy, NIRS can localize the epileptic focus or potentially predict seizure onset. Full article
(This article belongs to the Section Biomedical Optics)
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18 pages, 412 KiB  
Article
Enhancing Neuroplasticity Post Stroke: The Role of Cognitive–Behavioral Training
by Mohamed Rasmy Moursy, Abdulalim A. Atteya, Hoda M. Zakaria, Zizi M. Ibrahim, Olfat Ibrahim Ali, Nouf H. Alkhamees, Mye A. Basheer and Noura A. Elkafrawy
Brain Sci. 2025, 15(4), 330; https://doi.org/10.3390/brainsci15040330 - 22 Mar 2025
Viewed by 822
Abstract
Background: Stroke is a primary cause of adult disability and often causes cognitive impairment. Rehabilitation interventions aim to enhance patients’ cognitive abilities, thereby addressing care needs, improving quality of life, and optimizing performance in compromised functions. Objective: To evaluate the impact [...] Read more.
Background: Stroke is a primary cause of adult disability and often causes cognitive impairment. Rehabilitation interventions aim to enhance patients’ cognitive abilities, thereby addressing care needs, improving quality of life, and optimizing performance in compromised functions. Objective: To evaluate the impact of incorporating cognitive–behavioral training (CBT) into a selected exercise program on cortical reorganization and cognitive recovery in post-stroke patients. Methods: Thirty post-stroke patients of both sexes (27 male and 3 female) aged from 40 to 65 years were randomly divided into two groups: the study group (n = 15) received CBT combined with a selected exercise program including weight-bearing, balance, and aerobic exercises, while the control group (n = 15) underwent the selected exercise program only. All participants engaged in an 8-week intervention with three sessions per week. Cortical reorganization was measured using quantitative electroencephalography (QEEG) at electrode sites F3, F4, T5, and T6, and cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) and RehaCom, focusing on memory, attention, concentration, logical reasoning, and reaction behavior. Assessments were carried out for all patients before and after the 8-week treatment program. Results: Improvements were assessed through three key measures: QEEG, the MoCA, and RehaCom. Post-intervention, the study group demonstrated a significantly higher (alpha + beta)/(delta + theta) ratio at F3, F4, T5, and T6 (p < 0.01), indicative of enhanced cortical reorganization. MoCA scores increased by 16.98% in the study group compared to 7.40% in the control group (p < 0.01). Additionally, RehaCom assessments revealed marked improvements in memory, attention, logical reasoning, and reaction behavior in the study group (p < 0.01). Conclusions: Integrating cognitive–behavioral training with a selected exercise program significantly enhances cortical reorganization and cognitive recovery in post-stroke patients. These findings suggest that adding CBT to rehabilitation protocols can effectively address deficits in memory and attention, ultimately improving functional outcomes. Full article
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17 pages, 268 KiB  
Article
Effect of Transcranial Direct Current Stimulation on Memory and Emotional Recovery in Patients with Stroke and Traumatic Brain Injury: A Prospective, Multicenter, Interventional Pilot Study
by Marta Szczepańska, Zofia Twardochleb, Maciej Miś, Marcin Miś, Adam Druszcz, Małgorzata Paprocka-Borowicz and Joanna Rosińczuk
J. Clin. Med. 2025, 14(6), 2083; https://doi.org/10.3390/jcm14062083 - 19 Mar 2025
Viewed by 537
Abstract
Background/Objectives: Emotional and cognitive impairments are prevalent in patients with acute ischemic stroke (AIS) and traumatic brain injury (TBI), significantly affecting their quality of life and recovery potential. Transcranial direct current stimulation (tDCS) has emerged as a promising non-invasive method to enhance neurorehabilitation [...] Read more.
Background/Objectives: Emotional and cognitive impairments are prevalent in patients with acute ischemic stroke (AIS) and traumatic brain injury (TBI), significantly affecting their quality of life and recovery potential. Transcranial direct current stimulation (tDCS) has emerged as a promising non-invasive method to enhance neurorehabilitation outcomes by modulating neural activity. Methods: This prospective, open-label, multicenter interventional study included 100 participants (50 AIS, 50 TBI) who underwent 10 sessions of tDCS. Emotional states, depression levels, and memory and learning outcomes were assessed pre- and post-intervention using the UWIST Mood Adjective Checklist (UMACL), Depression Measurement Questionnaire (DMQ), Benton Visual Retention Test (BVRT), and Brain Damage Diagnostic Test (BDDT). Results: Significant improvements in emotional states were observed post-tDCS. Hedonic tone increased (AIS: 2.5 to 5 stens; TBI: 1.5 to 4 stens), while tension arousal decreased (AIS: 8 to 6 stens; TBI: 8 to 6 stens; all p < 0.001). Depression levels dropped significantly, with the overall depression index decreasing from 131 to 100 points in AIS and from 126 to 104 points in TBI (both p < 0.001). Memory and learning scores improved significantly, evidenced by increased correct responses and reduced errors in BVRT and BDDT tests (all p < 0.001). Conclusions: tDCS effectively improved emotional states, reduced depression levels, and enhanced cognitive functions in AIS and TBI patients. These findings support the integration of tDCS into neurorehabilitation protocols, with further research needed to explore long-term benefits and individualized treatment strategies. Full article
(This article belongs to the Special Issue Clinical Perspectives in Stroke Rehabilitation)
20 pages, 3281 KiB  
Review
Gastrointestinal Dysfunction and Dysbiosis in Ischemic Stroke: Opportunities for Therapeutic Intervention
by Rhiannon V. Macom and Candice M. Brown
Pharmaceuticals 2025, 18(3), 320; https://doi.org/10.3390/ph18030320 - 25 Feb 2025
Viewed by 685
Abstract
Although strokes originate in the brain, it is now widely appreciated that peripheral organ systems are also impacted by stroke. The gastrointestinal system is one peripheral organ system that is impaired during ischemic stroke. This impairment results in numerous complications, which impede post-stroke [...] Read more.
Although strokes originate in the brain, it is now widely appreciated that peripheral organ systems are also impacted by stroke. The gastrointestinal system is one peripheral organ system that is impaired during ischemic stroke. This impairment results in numerous complications, which impede post-stroke recovery. Many of the gastrointestinal mechanisms that contribute to the pathophysiology of ischemic stroke remain poorly understood. This review will highlight the molecular and cellular mechanisms underlying gastrointestinal outcomes in stroke by focusing on the complex interactions that largely occur in the small intestine. The final portion of this review will focus on therapeutic interventions that target the gut as a strategy to prevent or delay functional impairment and cognitive disability in stroke patients. Full article
(This article belongs to the Special Issue Emerging Therapeutic Candidates for Stroke Treatment)
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24 pages, 5261 KiB  
Article
Novel Robotic Balloon-Based Device for Wrist-Extension Therapy of Hemiparesis Stroke Patients
by Klaudia Marek, Aleksandra Olejniczak, Elżbieta Miller and Igor Zubrycki
Sensors 2025, 25(5), 1360; https://doi.org/10.3390/s25051360 - 23 Feb 2025
Viewed by 856
Abstract
Upper-limb paresis is one of the main complications after stroke. It is commonly associated with impaired wrist-extension function. Upper-limb paresis can place a tremendous burden on stroke survivors and their families. A novel soft-actuator device, the Balonikotron, was designed to assist in rehabilitation [...] Read more.
Upper-limb paresis is one of the main complications after stroke. It is commonly associated with impaired wrist-extension function. Upper-limb paresis can place a tremendous burden on stroke survivors and their families. A novel soft-actuator device, the Balonikotron, was designed to assist in rehabilitation by utilizing a balloon mechanism to facilitate wrist-extension exercises. This pilot study aimed to observe the functional changes in the paralyzed upper limb and improvements in independent and cognitive functions following a 4-week regimen using the device, which incorporates a multimedia tablet application providing audiovisual feedback. The device features a cardboard construction with a hinge at wrist level and rails that guide hand movement as the balloon inflates, controlled by a microcontroller and a tablet-based application. It operates on the principle of moving the hand at the wrist by pushing the palm upwards through a surface actuated by a balloon. A model was developed to describe the relationship between the force exerted on the hand, the angle on hinge, the pressure within the balloon, and its volume. Experimental validation demonstrated a Pearson correlation of 0.936 between the model’s force predictions and measured forces, supporting its potential for real-time safety monitoring by automatically shutting down when force thresholds are exceeded. A pilot study was conducted with 12 post-stroke patients (six experimental, six control), who participated in a four-week wrist-extension training program. Clinical outcomes were assessed using the Fugl–Meyer Assessment for the Upper Extremity (FMA-UE), Modified Rankin Scale (mRS), Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MOCA), wrist Range of Motion (ROM), and Barthel Index (BI). Statistically significant results were obtained for the Barthel index (p < 0.05) and FMA-UE, indicating that the experimental use of the device significantly improved functional independence and self-care abilities. The results of our pilot study suggest that the Balonikotron device, which uses the principles of mirror therapy, may serve as a valuable adjunct to conventional rehabilitation for post-stroke patients with hemiparetic hands (BI p = 0.009, MMSE p = 0.151, mRS p = 0.640, FMA-UE p = 0.045, MOCA p = 0.187, ROM p = 0.109). Full article
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12 pages, 1180 KiB  
Article
Novel Insights into Viewer-Centered Versus Stimulus-Centered Hemispatial Neglect: A Cross-Sectional Behavioral and Imaging Study of Acute Stroke
by Ashley Raman, Andreia V. Faria, Michael Colavito and Argye E. Hillis
Brain Sci. 2025, 15(2), 208; https://doi.org/10.3390/brainsci15020208 - 17 Feb 2025
Viewed by 609
Abstract
Background/Objectives: Hemispatial neglect is common after stroke but is often evaluated only after right hemisphere (RH) stroke. We sought to determine the prevalence of two types of neglect, viewer-centered neglect (VCN) and stimulus-centered neglect (SCN), after left hemisphere (LH) and RH strokes. Additionally, [...] Read more.
Background/Objectives: Hemispatial neglect is common after stroke but is often evaluated only after right hemisphere (RH) stroke. We sought to determine the prevalence of two types of neglect, viewer-centered neglect (VCN) and stimulus-centered neglect (SCN), after left hemisphere (LH) and RH strokes. Additionally, we identified lesion load in each vascular territory and areas of hypoperfusion, estimated with FLAIR hyperintense vessels (FVHs) that contribute to neglect. Methods: A series of 233 stroke patients (73 LH and 160 RH) were administered a task to detect VCN and SCN and received brain MRI within 5 days of onset. We used multivariable logistic regression to identify vascular territories where lesion load and/or hypoperfusion contributed to each type of neglect. Results: While VCN was more prevalent after RH stroke, SCN occurred at a similar rate after LH and RH stroke. In RH stroke, lesion load in the middle cerebral artery occipital region and anterior cerebral artery territory and age predicted left VCN, whereas parietal hypoperfusion independently predicted left SCN. In LH stroke, lesion load across regions and age predicted right VCN, while lesion load in posterior cerebral artery occipital and anterior cerebral artery regions, as well as age, predicted right SCN. The addition of information about hypoperfusion improved the prediction of both VCN and SCN. Conclusions: VCN and SCN are each common after RH stroke, and SCN is common after LH stroke. Each type of neglect is accounted for by distinct areas of infarct and hypoperfusion. Results will aid in the detection of neglect after stroke and may guide reperfusion interventions to improve neglect. Full article
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17 pages, 5031 KiB  
Article
Imipramine, an Acid Sphingomyelinase Inhibitor, Promotes Newborn Neuron Survival in the Hippocampus After Seizure
by Song Hee Lee, Hyun Wook Yang, Beom Seok Kang, Min Kyu Park, Dong Yeon Kim, Hong Ki Song, Hui Chul Choi, Minwoo Lee, Bo Young Choi, Dae-Soon Son and Sang Won Suh
Cells 2025, 14(4), 281; https://doi.org/10.3390/cells14040281 - 14 Feb 2025
Viewed by 758
Abstract
Epilepsy, a chronic neurological disorder, is triggered by various insults, including traumatic brain injury and stroke. Acid sphingomyelinase (ASMase), an enzyme that hydrolyzes sphingomyelin into ceramides, is implicated in oxidative stress, neuroinflammation, and neuronal apoptosis. Ceramides, which have pro-apoptotic properties, contribute to oxidative [...] Read more.
Epilepsy, a chronic neurological disorder, is triggered by various insults, including traumatic brain injury and stroke. Acid sphingomyelinase (ASMase), an enzyme that hydrolyzes sphingomyelin into ceramides, is implicated in oxidative stress, neuroinflammation, and neuronal apoptosis. Ceramides, which have pro-apoptotic properties, contribute to oxidative damage and lysosomal dysfunction, exacerbating neuronal injury. This study investigates the role of ASMase in epilepsy, hypothesizing that seizure activity upregulates ASMase, increasing ceramide levels, DNA damage, and neuronal apoptosis. We employed a pilocarpine-induced rat seizure model and examined the effects of imipramine, an ASMase inhibitor, administered intraperitoneally (10 mg/kg) for four weeks post-seizure induction. Histological and cognitive analyses showed that while imipramine did not prevent early neuronal death within the first week, it significantly reduced markers of neuronal apoptosis by four weeks. Imipramine also promoted hippocampal neurogenesis and preserved cognitive function, which is often impaired following seizures. These findings suggest that ASMase inhibition could mitigate neuronal apoptosis and improve cognitive recovery after seizures. Imipramine may serve as a promising therapeutic strategy for epilepsy-associated neuronal damage and cognitive deficits. Further studies should delineate the molecular mechanisms of ASMase inhibition and evaluate its long-term efficacy in addressing epilepsy-related neurodegeneration and functional impairments. Full article
(This article belongs to the Special Issue Advances in Neurogenesis: 3rd Edition)
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13 pages, 627 KiB  
Study Protocol
Functional Connectivity and MRI Radiomics Biomarkers of Cognitive and Brain Reserve in Post-Stroke Cognitive Impairment Prediction—A Study Protocol
by Hanna Maria Dragoș, Adina Stan, Livia Livinț Popa, Roxana Pintican, Diana Feier, Nicu Cătălin Drăghici, Dragoș-Cătălin Jianu, Diana Chira, Ștefan Strilciuc and Dafin F. Mureșanu
Life 2025, 15(1), 131; https://doi.org/10.3390/life15010131 - 20 Jan 2025
Viewed by 1481
Abstract
Acute ischemic stroke (AIS) is frequently associated with long-term post-stroke cognitive impairment (PSCI) and dementia. While the mechanisms behind PSCI are not fully understood, the brain and cognitive reserve concepts are topics of ongoing research exploring the ability of individuals to maintain intact [...] Read more.
Acute ischemic stroke (AIS) is frequently associated with long-term post-stroke cognitive impairment (PSCI) and dementia. While the mechanisms behind PSCI are not fully understood, the brain and cognitive reserve concepts are topics of ongoing research exploring the ability of individuals to maintain intact cognitive performance despite ischemic injuries. Brain reserve refers to the brain’s structural capacity to compensate for damage, with markers like hippocampal atrophy and white matter lesions indicating reduced reserve. Cognitive reserve involves the brain’s ability to optimize performance and use alternative networks to maintain function. Advanced methods of MRI and EEG processing may better assess brain reserve and cognitive reserve, with emerging predictive models integrating these measures to improve PSCI prediction. This article provides the design of a hospital-based study investigating the predictive role of functional connectivity and MRI radiomics in assessing PSCI occurrence one year after AIS. One hundred forty-four patients will be enrolled following strict inclusion/exclusion criteria. The patients will undergo comprehensive assessments, including neuropsychological testing, brain MRI, and quantitative EEG (QEEG), across four visits over a year. The primary outcome will be PSCI occurrence, and it will be assessed at six and twelve months after AIS. Secondary outcomes will include PSCI severity, recurrent AIS, and mortality. Statistical analyses will be performed to identify predictive factors using Cox proportional hazards models, and predictive models based on QEEG, MRI radiomics, and clinical data will be built. Early detection of AIS patients prone to developing PSCI might outline more effective therapeutic approaches, reducing the social and economic burden of ischemic stroke. Full article
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28 pages, 15397 KiB  
Article
Mechanism of P-Hydroxy Benzyl Alcohol Against Cerebral Ischemia Based on Metabonomics Analysis
by Tian Xiao, Xingling Yu, Jie Tao, Jiaoyang Tan, Zhourong Zhao, Chao Zhang and Xiaohua Duan
Int. J. Mol. Sci. 2025, 26(1), 317; https://doi.org/10.3390/ijms26010317 - 1 Jan 2025
Viewed by 3553
Abstract
Stroke is the leading cause of death and disability worldwide, with ischemic stroke accounting for the majority of these. HBA is the active ingredient in Gastrodia elata and has potential therapeutic effects on central nervous system diseases. In this study, the cell model [...] Read more.
Stroke is the leading cause of death and disability worldwide, with ischemic stroke accounting for the majority of these. HBA is the active ingredient in Gastrodia elata and has potential therapeutic effects on central nervous system diseases. In this study, the cell model of cerebral ischemia was replicated by the culture method of oxygen-glucose deprivation/reoxygenation, and the rat model of vascular dementia was established by the two-vessel occlusion method. Metabolomics technology was employed to analyze the metabolic changes in ischemic neurons induced by HBA, and potential therapeutic targets were verified. The protective effects of HBA on ischemic neurons and their mitochondria were examined through multiple indicators, and the related mechanisms were verified. HBA can improve post-ischemic cognitive impairment in rats, and its mechanism is related to the regulation of the choline-activated phospholipase D2/Sirtuin 1/peroxisome proliferator-activated receptor-γ coactivator 1α pathway to improve mitochondrial function and reduce autophagic activity to maintain mitochondrial homeostasis. It is concluded that HBA has a protective effect on neuronal damage and cognitive impairment caused by cerebral ischemia by regulating key metabolites and signaling pathways, and that it provides a new molecular target for the treatment of cerebral ischemia. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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30 pages, 596 KiB  
Review
The Role of Mirror Therapy in the Rehabilitation of the Upper Limb’s Motor Deficits After Stroke: Narrative Review
by Ioannis Ventoulis, Kyriaki-Rafaela Gkouma, Soultana Ventouli and Effie Polyzogopoulou
J. Clin. Med. 2024, 13(24), 7808; https://doi.org/10.3390/jcm13247808 - 20 Dec 2024
Cited by 1 | Viewed by 3007
Abstract
Stroke is one of the leading causes of death and disability worldwide and poses a tremendous socioeconomic burden upon individuals, countries and healthcare systems. It causes debilitating symptoms and thus interferes with many aspects of the patient’s life, including physical functioning, cognition, emotional [...] Read more.
Stroke is one of the leading causes of death and disability worldwide and poses a tremendous socioeconomic burden upon individuals, countries and healthcare systems. It causes debilitating symptoms and thus interferes with many aspects of the patient’s life, including physical functioning, cognition, emotional status, activities of daily living, social reintegration and quality of life. Post-stroke patients frequently experience functional motor disabilities of the upper limb, which restrict autonomy and self-efficacy and cause limitations in engagement with activities and social participation, as well as difficulties in performing important occupations. It is therefore not surprising that motor impairment or loss of motor function of the upper limb is one of the most devastating sequelae of stroke. On these grounds, achieving optimal functioning of the upper limb after stroke remains a fundamental goal of stroke rehabilitation. Mirror therapy (MT) represents one of the several rehabilitation techniques used for restoring the upper limb’s motor function after a stroke. However, conflicting results about the role of MT in the rehabilitation of the upper limb’s motor deficits have been reported in the literature. Accordingly, the aim of this narrative review is to summarize existing evidence regarding the effects of MT on the upper limb’s motor function in post-stroke patients and to further explore its role when applied in different phases of stroke. Full article
(This article belongs to the Section Clinical Rehabilitation)
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