Physical activity-associated extracellular vesicles inhibit inflammagen-induced microglial activation.

Functional and structural respiratory impairment in cerebral palsy- GMFCS IV and V: Insights from ultrasound and inspiratory muscle testing.

PPARγ activation by leriglitazone counteracts neurodegeneration and neuroinflammation in a disease-relevant mouse model of COASY dysfunction.

The protein co-chaperone STI-1 impacts motor function in C. elegans upon developmental methylmercury exposure.

Dynamic changes in brain structure-function correspondence in typical and atypical upper limb motor recovery after stroke.

Voice analysis as a digital biomarker: A machine learning approach for automated multiple sclerosis classification.

Inhibition of the NFATc2/FKBP5 axis alleviates microglial neuroinflammation by regulating arachidonic acid metabolism in Parkinson's disease.

Elucidating the role of right dorsolateral prefrontal cortex in cognitive-motor interference: Polarity-specific effects of transcranial direct current stimulation.

Modified Constraint-Induced Movement Therapy (mCIMT) has demonstrated significant potential in rehabilitating lower extremity motor impairments following stroke. However, mCIMT's application is often limited by the need for specialized devices to constrain the non-affected extremity and longer training duration. Constraint Standing Training (CST) is a novel variation of mCIMT that addresses these limitations by eliminating the need for constraining devices and reducing training time, thereby enhancing its feasibility for clinical implementation. Despite these advantages, the specific effects of CST on balance and gait in stroke patients remain underexplored. This study will use a randomized, controlled, single-blinded design. Fifty stroke patients in the chronic phase, with gait disabilities and the ability to stand independently, will be randomly assigned to either the CST group or a control group using a computer-generated randomization sequence. Exclusion criteria include physiological or cognitive impairments that may hinder evaluation or training. Both groups will undergo daily 1-h training sessions, five times per week, for 8weeks. The CST group will undergo sequential standing training using shaping strategies from a single plane to multiple planes, while the control group will receive conventional intensive training, which includes balance and gait exercises commonly used in clinical practice. Assessments will be carried out at baseline (T0), mid-intervention (T1), post-intervention (T2), and 1 month follow-up (T3). The primary outcome of this trial is the Timed Up and Go (TUG) test. Secondary outcomes include the 10-Meter Walk Test, 6-Minute Walk Test, Berg Balance Scale, three-dimensional gait analysis, and surface electromyography. Missing data will be handled using multiple imputation by chained equations. Data will be analyzed using two-way repeated measures ANOVA or generalized estimating equations to determine differences and identify clinically relevant changes. This protocol provides detailed CST methods to guide future research and clinical application. The study employs a randomized controlled trial design to robustly evaluate CST's effects on balance and gait in hemiparetic stroke patients. CST's sequential, multi-plane exercises offer a potentially practical alternative. However, larger, multi-center trials are recommended for future validation. This trial is registered at www.chictr.org.cn. ChiCTR2400086282. Date of registration: 27 June 2024.

Neuromuscular disorders (NMDs) are a heterogeneous group of conditions characterized by progressive muscle weakness, motor impairment and risk of malnutrition, affecting the quality of life (QoL) of patients. While pharmacological treatments are essential for the management of symptoms, the role of diet, nutrition and other lifestyle factors remains underexplored. This narrative systematic review, performed on PubMed, Web of Science, and Scopus following PRISMA guidelines, aimed to investigate the relationship between lifestyle, the progression of NMDs and the QoL. A total of 30 studies (n=5055 patients) met inclusion criteria. According to our search strategy, the most representative lifestyle factors were diet (70%), physical activity (53.3%) and emotional perception and care (36.7%); 7 papers (23.3%) evaluated three or more lifestyle aspects. Overall, both quantitative and qualitative deficiencies emerged: calories, proteins, lipids and fibres, as well as vitamin C, vitamin E, zinc, selenium and calcium were lower than recommended. A reduced consumption of fruits, vegetables, legumes, nuts and seeds, replaced by ultra-processed foods, was detected. Diets optimised for calorie and nutrients intake, rich in anti-inflammatory foods, have shown benefits both in mitigating oxidative stress and muscle degeneration. Regarding other aspects of lifestyle, although physical activity was associated with improved motor performance and QoL, adherence was low, particularly among females. Negative emotional status emerged as a critical factor influencing patients' overall well-being. Even in the most complex neuromuscular disease settings, addressing nutrition and dietary habits, in the context of lifestyle, could support patients and their families throughout the disease course and improve their QoL.

Introduction Stroke represents a leading global cause of disability, often causing motor impairments that diminish quality of life. Neurorehabilitation that leverages human motor learning (HML) theories is crucial for post-stroke recovery. Therapists guide repetitive practice that supports re-learning, and they adjust assistance to individual needs and progress. Robot-assisted rehabilitation has advanced this approach, and recent work shows AI-driven systems can improve adaptability to patient behavior beyond earlier technologies. However, notably few systems aim to explicitly replicate therapist assistance from the perspective that physical assistance is a motor skill in itself. Methodology This narrative review examines advances in AI-driven stroke rehabilitation, analyzing how systems facilitate HML within patients and how their models approximate HML mechanisms. By breaking down the four core HML processes to their essentials, using Marr's tri-level hypothesis, we compare machine learning models used within rehabilitation systems to the HML processes. Results Many of the reviewed systems appear to primarily facilitate use-dependent and sensory-prediction error-based learning, with limited facilitation of reinforcement learning or strategy-based learning. Explicit modeling of therapist HML within control frameworks appears relatively rare. Implicitly, many of the reviewed AI systems functionally represent one or two HML processes. Conclusion Current research often considers HML primarily in patients, whereas therapists' own HML likely underpins the robustness and adaptability of clinical assistance. Interpreting the reviewed rehabilitation systems through this lens highlights opportunities for therapist-inspired multi-process controllers, improved benchmarking with clinical scales, longitudinal retention studies, and AI-driven closed-loop neuromodulation to enhance personalization, adaptability, and outcomes, and to support clinical translation into routine practice.

BackgroundUpper extremity rehabilitation is critical for individuals with neurological disorders such as Parkinson's disease, where motor impairments significantly affect daily functionality.ObjectiveThis study presents the design and prototyping of a novel rehabilitation glove aimed at improving hand and wrist motor recovery through gamified therapy.MethodsThe proposed glove features wireless communication via a Wi-Fi network, adaptability to various hand sizes, and an integrated strength training mechanism using resistance bands and metal hooks. The glove consists of a lightweight forearm frame, a palm component, and a textile glove with embedded mechanical connectors, all designed based on anthropometric data. 3D printing techniques were employed using PLA and flexible TPU materials to create a modular, low-cost, and comfortable structure. The system interfaces with an interactive game, allowing users to control an avatar (bee) through hand movements, promoting motivation and active engagement.ResultsThe prototype effectively addresses key limitations of previous rehabilitation systems, including mobility, comfort, adaptability, and functionality.ConclusionThe proposed rehabilitation glove offers a promising solution for home-based neurorehabilitation.

Abstract Decoding the activity of the nervous system is a critical challenge in neuroscience and neural interfacing. In this study, we present a neuromuscular recording system that enables large-scale sampling of muscle activity using microelectrode arrays with over 100 channels embedded in forearm muscles. These arrays captured intramuscular high-density signals that were decoded into patterns of activation of spinal motoneurons. In two healthy participants, we recorded high-density intramuscular activity during single- and multi-digit contractions, revealing distinct motoneuron recruitment patterns specific to each task. Based on these patterns, we achieved perfect classification accuracy (100%) for 12 single- and multi-digit tasks and over approximately 96% accuracy for up to 16 tasks, significantly outperforming state-of-the-art electromyogram classification methods. This intramuscular high-density system and classification method represent an advancement in neural interfacing, with the potential to improve human–computer interaction and the control of assistive technologies, particularly for replacing or restoring impaired motor function.

Propagation of gut-injected AAV2/1-Htt171-82Q to the brain induces Huntington's disease-like pathology.

Peripheral nerve injuries (PNI) often induce severe motor and sensory impairments, subsequent muscle atrophy, and even permanent disability. Autologous nerve grafting, the clinical gold standard for PNI repair, is limited by donor site morbidity and graft shortage, while conventional nerve guidance conduits (NGCs) only provide physical guidance and fail to reconstruct the bioactive microenvironment essential for nerve regeneration. To address these limitations, we fabricated chitosan NGCs functionalized with cryo-shocked neural stem cells (Cryo-NSC NGCs) as a tissue-specific factor pool, via seeding NSCs onto the conduit lumen for short-term expansion followed by liquid nitrogen cryo-shock. Cryo-NSC NGCs sustainably release neurotrophic factors, enhance neural cell adhesion and neuronal differentiation, with the average axon length reaching 9.42-fold that of the blank control, outperforming cryo-shocked MSC-functionalized NGCs as validated by proteomic enrichment of neural regeneration-related proteins. In a rat 10-mm sciatic nerve defect model, Cryo-NSC NGCs effectively promoted axonal regeneration, myelination and vascularization, restored motor and sensory functions with nerve conduction recovery approaching autologous grafts, and exhibited excellent biocompatibility without excessive inflammation or organ damage. Collectively, Cryo-NSC NGCs provide a safe, efficient and translational platform for peripheral nerve repair. STATEMENT OF SIGNIFICANCE: 1. Cryo-shocked neural stem cells (NSCs) retain a complete, native repertoire of bioactive factors to deliver sustained, tissue-specific bioactive support directly to injured peripheral nerves. 2. Neuro-specific bioactive proteins in Cryo-NSCs synergistically enhance neural cell adhesion and drive a 9.42-fold increase in axonal elongation, significantly outperforming cryo-shocked mesenchymal stem cells (Cryo-MSCs). 3. Cryo-NSC-functionalized nerve guidance conduits (NGCs) effectively repair 10-mm sciatic nerve defects, with favorable behavioral, electrophysiological, and histological outcomes, offering a promising translational strategy for peripheral nerve injury treatment.

When recommending suitable ways for people with Parkinson's disease (PD) to increase their physical activity, healthcare professionals and caregivers often base their advice on observable motor impairments. Yet we might also consider the dimension of happiness. A 66-year-old former professional water polo player with longstanding PD felt completely freed from his symptoms while swimming, with a sustained post-exercise benefit. His experience in the water was a feeling of happiness. He noticeably worsened on days when he did not swim. However, objective video analysis found no corresponding motor improvement during swimming, which remained significantly impaired due to poor interlimb coordination and ineffective leg movements. This discrepancy underscores the importance of recognising meaningful subjective benefits, including reduced tension and stress that may not be captured by motor assessments alone. In addition to safety concerns, including drowning risk during swimming, exercise recommendations should also consider subjective patient-reported benefits.

Introduction Motor impairments are highly prevalent in children with Autism Spectrum Disorder (ASD) and have been associated with reduced functional independence, participation, and sociocommunicative development. Despite the growing body of evidence supporting the relevance of motor functioning in ASD, motor-based interventions remain underrepresented in high-quality randomized clinical trials. The Global Integration Method (Método de Integração Global - MIG) is an intensive, interdisciplinary intervention grounded in the theories of predictive coding and embodied cognition, with emphasis on motor organization, proprioceptive stimulation, and generalization of functional skills in real-life contexts. Objective The aim of this study is to evaluate the effectiveness of the MIG program in improving fundamental motor skills and achieving functional goals, compared with conventional physiotherapy and psychological interventions, in children with ASD. Secondary objectives are to investigate the effects of MIG on balance, sociocommunicative skills, and motor performance. Methods and analysis This is a three-arm randomized controlled trial with concealed allocation and blinded outcome assessors. Sixty-six children with ASD, aged 6 to 12 years, classified as requiring level 1 or 2 support, will be randomized into one of three groups: (I) MIG program, (II) conventional psychological intervention, and (III) conventional motor physiotherapy. Interventions will last five weeks. Assessments will be conducted at baseline, immediately post-intervention, and three months after completion. Primary outcomes include fundamental motor skills and functional goal attainment. Secondary outcomes include measures of balance, sociocommunicative skills, and motor performance. Data will be analyzed using linear mixed-effects models, following the intention-to-treat principle. Ethics and dissemination The protocol was approved by the Research Ethics Committee of the Faculty of Medical Sciences of Minas Gerais, Brazil (Approval No. 7,456,658). Written informed consent will be obtained from parents or legal guardians, and assent will be sought from participating children when developmentally appropriate. Study findings will be disseminated through peer-reviewed publications, conference presentations, and reports to participating families and institutions. Clinical Trial Registration This protocol was prospectively registered in the Brazilian Registry of Clinical Trials https://ensaiosclinicos.gov.br/rg/RBR-7r6n8zd, identifier U1111-1326-2272.

Genetically mediated increased expression of syntaxin-6, a SNARE protein involved in intracellular protein trafficking, is a proposed risk mechanism for progressive supranuclear palsy and sporadic prion disease. Increased syntaxin-6 protein levels are also causally associated with Alzheimer's disease, suggesting it may have shared roles across multiple neurodegenerative diseases. However, no study has validated its functional role in tauopathies. To validate a role for syntaxin-6 in tauopathy pathogenesis, we knocked out syntaxin-6 in humanised P301S tauopathy mice. Mice underwent longitudinal rotarod testing, gait analysis, frailty and weight assessment, with neuropathological, biochemical and pathological analyses at 3 and 5months. Stx6+/+;hTauP301S/P301S mice showed motor impairment from 1month of age, which was partially rescued by syntaxin-6 knockout from months 1 to 4, with additional protection of gait at 5.5months. Physiologically, syntaxin-6 knockout exerted a protective effect on weight trajectories and measures of frailty. Reduced neurodegeneration in the superficial cortex was observed at 3months, as well as higher synaptic coverage at 5months of age, supporting preserved neuropathological measures related to function. We further observed localised increases in tau pathology in the spinal cord and defined brain regions in young Stx6-/-;hTauP301S/P301S mice, despite total tau levels being comparable, in keeping with altered trafficking of pathological tau species with syntaxin-6 knockout. Despite a partial, early phenotypic rescue of functional measures, terminal endpoint comparisons were confounded by a 20% weight loss culling rule, as knockout mice maintained higher absolute weight. Taken together, this study functionally validates a role for syntaxin-6 in tauopathy pathogenesis, with syntaxin-6 knockout resulting in an early protective effect on multiple disease-relevant phenotypes in a humanised tauopathy model.

Metachromatic leukodystrophy (MLD) is arare lysosomal storage disorder characterized by progressive white matter demyelination. Quantification of demyelinated white matter on MRI-typically expressed as the demyelination load-serves as akey imaging biomarker of disease burden, enabling objective monitoring beyond visual rating scales. However, current semi-automated pipelines are limited by manual interaction, pediatric brain variability, and differences in MRI acquisition. This study aimed to develop and validate aself-configuring convolutional neural network (CNN) for automated segmentation of demyelinated white matter in MLD and to compare its performance with aconventional semi-automated method across heterogeneous MRI datasets. An nnU-Net was trained on 189 3D T1- and axial T2-weighted scans from 35MLD patients using visually controlled conventional masks as ground truth. Independent testing was performed on 130 scans (73high-resolution 3D, 57lower-resolution 2D T1-weighted) from 49patients. Performance was assessed by Dice coefficient, Bland-Altman bias, correlation with Gross Motor Function Classification (GMFC-MLD), MLD MRI severity score, longitudinal consistency, and qualitative review of outliers. CNN-based segmentation showed strong spatial agreement with the reference method, with amedian Dice coefficient of 0.82 for 3D T1-weighted scans and 0.75 for 2D scans. Volumetric bias was minimal on Bland-Altman analysis. CNN-derived demyelination load correlated significantly with motor impairment (rS = 0.38 for 3D and r = 0.56 for 2D; both p < 0.001) and showed astronger association with the MLD MRI severity score than conventional segmentation (3D: rS = 0.48 vs. 0.28; 2D: rS = 0.83 vs. 0.29). Correlations with clinical status were slightly lower (CNN: rS = 0.38, p < 0.001; conventional: (rS = 0.26, p < 0.025)) Longitudinal analyses demonstrated stable, monotonic changes over time, and qualitative review revealed fewer boundary misclassifications. The nnU-Net enables fast, reproducible, and clinically meaningful segmentation of demyelinated white matter in MLD. It generalizes across MRI protocols, correlates with motor function, and offers ascalable tool for standardized biomarker extraction in clinical trials and other leukodystrophies.

Neurodegenerative disorders are progressive and multifactorial diseases characterized by neuronal loss, synaptic dysfunction and cognitive and motor impairment. Major pathogenic mechanisms include abnormal protein aggregation, oxidative stress, mitochondrial dysfunction, neuroinflammation, excitotoxicity and disruption of brain barrier systems. Current pharmacological therapies primarily offer symptomatic relief and fail to halt disease progression, highlighting the need for multi-target neuroprotective strategies. Traditional Unani medicine provides a holistic framework for neurological health, emphasizing restoration of cerebral balance and systemic homeostasis. Abresham (Bombyx mori silk) and Ustukhuddus (Lavandula stoechas) are well-established Unani drugs traditionally used for neurological and neuropsychiatric disorders. Emerging analytical and preclinical evidence demonstrates that Abresham exerts neuroprotective effects through antioxidant, anti-inflammatory, mitochondrial-stabilizing, and neuromodulatory actions mediated by silk proteins such as fibroin and sericin. Ustukhuddus exhibits neuroprotection via modulation of GABAergic and cholinergic neurotransmission, suppression of neuroinflammation, and reduction of oxidative stress, largely attributed to its volatile oils and phenolic constituents. This review integrates contemporary mechanistic insights into neurodegeneration with traditional Unani knowledge to highlight the therapeutic potential of Abresham and Ustukhuddus as promising multi-target neuroprotective agents.