Improve Motor Function Research Articles

Inhibition of Pyroptosis by Hydroxychloroquine as a Neuroprotective Strategy in Ischemic Stroke.

Hydroxychloroquine (HCQ), a well-known antimalarial and anti-inflammatory drug, has demonstrated potential neuroprotective effects in ischemic stroke by inhibiting pyroptosis, a programmed cell death associated with inflammation. This study investigates the impact of HCQ on ischemic stroke pathology using both in vivo and in vitro models. In vivo, C57BL/6 mice subjected to middle cerebral artery occlusion (MCAO) were treated with HCQ. Neurological deficits, infarct volume, and the expression of pyroptosis markers were evaluated. The results demonstrated that HCQ significantly improved motor function and reduced infarct volume in the MCAO mouse model. In vitro, BV2 microglial cells exposed to lipopolysaccharide (LPS) and oxygen-glucose deprivation (OGD) were treated with HCQ. Western blot and immunofluorescence analyses revealed that HCQ effectively suppressed the expression of pyroptosis markers GSDMD and NLRP3 in both in vivo and in vitro models. These findings suggest that HCQ mitigates ischemic stroke damage by inhibiting pyroptosis, highlighting its potential as a therapeutic agent for ischemic stroke. This study provides novel insights into the molecular mechanisms by which HCQ exerts its neuroprotective effects, offering a promising new avenue for developing safe, cost-effective, and widely applicable stroke treatments. The potential of HCQ to modulate neuroinflammatory pathways presents a significant advancement in ischemic stroke therapy, emphasizing the importance of targeting pyroptosis in stroke management and the broader implications for treating neuroinflammatory conditions.Significance Statement Ischemic stroke remains a leading cause of disability and death globally, with limited effective treatments. This study reveals that HCQ significantly mitigates ischemic stroke damage by inhibiting pyroptosis, a form of programmed cell death. Using in vivo and in vitro models, HCQ was shown to improve motor function and reduce infarct volume, highlighting its potential as a neuroprotective agent. These findings offer a promising new therapeutic approach for ischemic stroke, emphasizing the importance of targeting pyroptosis in stroke treatment.

Neurodevelopmental benefits of judo training in preschool children: a multinational, mixed methods follow-up study

IntroductionIn our quasi-experimental study, we evaluated the neurodevelopmental impact of judo on young children (n = 182) aged 4–7 years, specifically focusing on primitive reflex integration. Participants were divided into judo and non-judo control groups, and assessments were conducted over 6 months across Hungary, Slovakia, and Austria.MethodsNeurodevelopmental changes were measured using Institute for Neuro-Physiological Psychology (INPP) and Physical and Neurological Examination for Soft Signs (PANESS) for children, while parents completed the Performance Skills Questionnaire (PSQ).ResultsAnalysis with Repeated Measures ANOVA (significance set at p < 0.05) revealed significant improvements in cognitive and motor performance in judo-practicing children compared to their non-judo counterparts. Furthermore, Spearman correlation analysis revealed that INPP and PANESS were effective in identifying neurodevelopmental changes, PSQ was not suitable as a simplified screening tool for parents, potentially due to its absence of items focused on primitive reflexes.ConclusionDespite the limitations of the study, our findings suggest that judo practice could foster central nervous system (CNS) maturation in young children, promoting the potential inclusion of judo in early childhood education programs.

Advances in Stem Cell Therapy: A Hope for Regenerative Medicine

Introduction Regenerative medicine has become a light at the end of the tunnel for countless patients who have suffered from diseases previously considered incurable. Stem cell therapy is central to this revolutionary progress and has already made huge advances in recent years. Stem cells have the potential to regenerate tissues, repair organs, and even modulate immune responses, making them a key to delivering innovative treatments for a broad spectrum of medical conditions. This editorial describes recent progress in stem cell therapy as well as its promise as a regenerative medicine[1]. Stem Cells have unique Properties. Stem cells have unique properties that make them of great value in therapeutic applications. This allows them to self-renew and differentiate into specialized cell types with immense possibilities of being used in treating degenerative diseases, tissue injuries, and even genetic disorders. Each type is classified broadly into embryonic stem cells (ESCs), adult stem cells (ASCs), and induced pluripotent stem cells (iPSCs) with particular advantages. For example, ESCs are pluripotent and can differentiate into almost any cell type, while the more accessible and less ethically controversial MSCs like the ASCs[2]. Pioneered most recently by Shinya Yamanaka, recent breakthroughs in iPSC technology have further revolutionized the field. IpsCs overcome many of the limitations of ESCs by reprogramming somatic cells into a pluripotent state. It has accelerated the development of patient-specific therapies – personalized regenerative solutions[3]. Stem Cell Therapy Success Stories Stem cell therapies have already had tremendous success in treating multiple different medical conditions. Therapies have also been shown to be effective in treating Parkinson’s disease, spinal cord injuries, and stroke in neurological disorders. Damaged neurons have been replaced with transplanted stem cells and lost functions have been restored[4]. While recent clinical trials using MSCs and iPSCs for stroke recovery have revealed improved motor function as well as reduced inflammation, they represent a great leap forward in this field. Repairing damaged heart tissue that results from myocardial infarction has been explored using cardiomyocyte transplantation from ESCs and iPSCs. In preclinical and clinical studies, these therapies not only support tissue regeneration but also enhance cardiac function and survival outcomes[5]. The differentiation of ESCs and iPSCs into insulin-secreting β cells for use in the treatment of type- 1 diabetes represents another major milestone in stem cell therapy. But β cells transplanted into the bloodstream can regulate blood glucose levels, and at last, this represents a realistic prospect of a cure[6, 7]. Unfortunately, hematopoietic stem cell transplantation (HSCT) remains the gold standard for treating blood-related disorders, such as leukemia, aplastic anemia, and immune deficiencies. HSCT has been further made safer and more effective by advances in gene editing technologies such as CRISPR-Cas9, which now allow for targeted genetic therapies. MSCs are being widely investigated in the orthopedic field for their potential to regenerate cartilage, bone, and muscle tissue. Stem cell therapy has shown a lot of promise in osteoarthritis, fractures, and tendon injuries, where the therapies help to speed up healing and reduce pain[8]. Challenges of Stem Cell Therapy Sure, the promise of stem cell therapy is undeniable, but a host of challenges must be overcome first to make it a mainstream clinical tool. Despite all of this, safety concerns remain paramount: tumorigenesis, immune rejection, and unintended differentiation. Equally important is standardization and regulation, which will help develop consistent protocols for stem cell isolation, culture, and transplantation with reproducible outcomes from clinical trials. In addition, stem cell therapies are very expensive, which limits access, especially in low and middle-income countries. However, ESCs have continued to raise ethical concerns, particularly in the area of ESCs, and therefore alternative sources such as iPSCs and adult stem cells are needed[9]. Future Directions Overcoming these challenges is a future challenge for bioengineering, nanotechnology, and gene editing. For example, 3D bio-printed tissues and organoids bring together stem cell technology and tissue engineering to provide functional tissues for transplantation. These innovations could change the way we deal with organ failure and more advanced medical conditions[10]. Conclusion Stem cell therapy enters into a new era of progressive continuous progress. With the continued expansion of clinical trials and increasing technology, stem cell therapies have the potential to transform the treatment landscape for many diseases and injuries. Still, there is plenty of work to be done, but the convergence of interdisciplinary innovations presents a strong foundation for hope. With the participation of scientists, clinicians, policymakers, and industry stakeholders, stem cell research can be translated into safe, effective, and accessible therapies benefiting millions of patients with the possibility to recover and improve their quality of life. Regenerative medicine has a promising future and stem cells are at the center of that progress. Through innovation and addressing current challenges, we can unleash the full power of stem cell therapies to provide transformative solutions to patients around the world.

Improving Motor Function in Adults with Parkinson’s Disease through Occupational Therapy and Rehabilitation

Improving Motor Function in Adults with Parkinson’s Disease through Occupational Therapy and Rehabilitation

Analysis of gene therapy encoding aromatic L-amino acid decarboxylase (AADC) enzyme in the treatment of Parkinson’s disease

Parkinson's Disease (PD), a progressive neurodegenerative disorder characterized by dopaminergic neuron degeneration, leads to motor and non-motor symptoms that significantly impair quality of life. Conventional treatments, such as levodopa, provide symptom relief but are associated with long-term complications and do not halt disease progression. This review systematically evaluates the efficacy and safety of gene therapy targeting the aromatic L-amino acid decarboxylase (AADC) enzyme in treating PD and AADC deficiency, focusing on sustained dopamine production and motor function improvement. A systematic literature review was conducted using databases like PubMed, Scopus, and Embase, covering studies published over the past 32 years. Out of 52 articles identified, 25 met inclusion criteria, providing data on motor outcomes, dopamine production, and safety profiles. Findings suggest that AADC gene therapy may offer a durable therapeutic approach, reducing reliance on conventional dopamine replacement therapies and mitigating related complications. This review highlights gene therapy's potential in clinical practice, emphasizing a shift towards targeted treatment strategies for dopamine-deficient neurodegenerative disorders. Further research should address long-term efficacy and safety across diverse patient groups. Limitations include potential selection bias and language restrictions.

The effects of telerehabilitation-based motor imagery training on motor imagery ability, motor function and physical performance in Duchenne muscular dystrophy

Purpose To explore the effects of telerehabilitation-based motor imagery (Tele-MI) training on motor imagery ability (MI), motor function, and performance in children with Duchenne muscular dystrophy (DMD). Methods The research involved twenty-three children with DMD and twelve healthy children. DMD cohort were randomized into two groups: treatment [Tele-MI training and telerehabilitation-based physiotherapy program (Tele-PTP), n = 12] and control (Tele-PTP, n = 11). MI ability [Kinesthetic and Visual Imagery Questionnaire-10 (KVIQ-10), Motor Imagery Questionnaire for Children (MIQ-C), mental chronometry tests], motor function [Motor Function Measure (MFM), North Star Ambulation Assessment, Four Square Step Test] and timed performance were assessed at baseline and after 8-week training. Results MI ability scores of DMD cohort were lower than healthy children. A large interaction effect was found for KVIQ-10 visual and total, MIQ-C internal visual and kinesthetic scores, and delta time of 10–meter walk test of mental chronometry (η2 > 0.14). The small-medium interaction effect was found in motor function and ambulation results (η2<0.14). Conclusions This study demonstrated that Tele-MI training improved MI ability of DMD cohort. The small-to-medium effects of Tele-MI training on motor function, particularly those involving the trunk, have demonstrated its potential as a complementary approach in rehabilitation to improve motor functions in children with DMD. Clinical Trial Registration Number and URL NCT06109103 (https://clinicaltrials.gov/study/NCT06109103?term=merve%20bora%20zereyak&rank=1)

Leucencephalopathy in Patients with Parkinson's Disease and Deep Brain Stimulation.

Leucencephalopathy (LE) is often detected on magnetic resonance imaging in elderly patients. These white matter lesions may interfere with lead trajectories for deep brain stimulation (DBS) in patients with Parkinson's disease (PD) and are associated with complications after DBS surgery. This study was conducted to assess the incidence of LE in PD patients and to evaluate correlations with complications after DBS surgery. A consecutive cohort of PD patients who underwent DBS surgery in the subthalamic nucleus (STN-DBS) was retrospectively analyzed. The presence and extent of LE were quantified using the Fazekas scale. Postoperative complications were extracted from the medical records. DBS efficacy was calculated using the side-specific motor symptom ratio (Unified Parkinson's Disease Rating Scale, Part III, postoperative stimulation ON/medication off divided by preoperative medication off) at 1-year follow-up. A total of 135 PD patients were included in the study. LE was detected in 35.6% (48/135) of the patients. In 87.7% (57/65), LE was mild, in 10.7% (7/65) moderate, and in 1.6% (1/65) severe. A higher incidence of mild to moderate LE did not correlate with postoperative hemorrhage or postoperative infection. There was no correlation of LE with stimulation efficacy (r = -0.05, P = 0.69) or with surgical index (r = -0.10, P = 0.35). Neither was the presence of mild to moderate LE associated with an increased risk for surgical complications, nor did it negatively impact the long-term improvement in motor function after DBS surgery in PD patients. Therefore, mild to moderate LE should not be considered a contraindication for DBS.

Hydrophobic Carbon Dots Prevent α‐Synucleinopathy and Suppress Neuroinflammation to Treat Parkinson's Disease

ABSTRACTThe aggregation of α‐synuclein (ɑ‐syn) coupled with overexpressed neuroinflammation instigates the degeneration of dopaminergic neurons, thereby aggravating the progression of Parkinson's disease (PD). Herein, we introduced a series of hydrophobic amino acid–based carbon dots (CDs) for inhibiting ɑ‐syn aggregation and mitigating the inflammation in PD neurons. Significantly, we show phenylalanine CDs (Phe‐CDs) could strongly bind with ɑ‐syn monomers and dimers via hydrophobic force, maintain their stability, and inhibit their further aggregates in situ and in vitro, finally conferring neuroprotection in PD by rescuing synaptic loss, ameliorating mitochondrial dysfunctions, and modulating Ca2+ flux. Importantly, Phe‐CDs demonstrate the ability to penetrate the blood–brain barrier (BBB), significantly improving motor performance in PD mice. Our findings suggest that Phe‐CDs hold great promise as a therapeutic agent for PD and the relative neurodegenerative disease.

Therapeutic impact of a benzofuran derivative on Aluminium chloride-induced Alzheimer's disease-like neurotoxicity in rats via modulating apoptotic and Insulin 1 genes

Neurodegenerative disorders such as Alzheimer’s disease (AD) are age-related and are fatal in advanced cases. There is a limited efficacy of drugs used for the management of these diseases. Herein, the neurotherapeutic efficacy of a benzofuran-derivative-7 (BF-7) was investigated. Aluminum chloride (AlCl3) was employed to induce AD-like brain toxicity in rats. The rats were divided into four groups: Negative control, AlCl3-induced AD rats (100 mg/kg body weight, orally), AlCl3-AD induced rats treated with BF-7 (10 mg/kg body weight, orally), AlCl3-AD-induced rats treated with the standard drug “Donepezil” (10 mg/kg body weight, orally). The behavioral performance was tested using a beam-balance test. Brain and serum acetylcholinesterase (AChE) activities and the brain levels of norepinephrine, dopamine (DA), and serotonin (5-HT) were measured. The genetic expression of Bcl-2, Bax, caspase-3, and insulin 1 were assayed. The histopathological imaging and the immunohistochemical evaluation of Glial Fibrillary Acidic Protein (GFAP) were investigated in the cerebral cortex. Treatment of AD-rats with BF-7 mitigated AlCl3-induced neurotoxicity by improving motor functions, counteracting apoptosis, and exerting cholinergic functions. In addition, the genetic expression of Insulin 1 was upregulated significantly in AD-induced rats treated with BF-7. This compound could be used as a promising candidate for neurotherapeutic drug discovery against AD or any other toxic brain disorders.

Novelle approach to simulating spinal cord stimulation during tSCS using CT images and FEM

Abstract Transcutaneous spinal cord stimulation (tSCS) offers non-invasive relief for chronic pain and improves motor function in spinal cord injured (SCI) patients. However, its mechanisms are not currently fully understood, and patientspecific factors, such as Body mass index (BMI) and age, complicate treatments. This paper aims to understand tSCS better by developing a novel Finite Element Model (FEM) of the human body using CT scans. Three subjects (sex, male, female, male. Age: 26, 27, 64. BMI: 38.9, 24.1, 28.4) underwent a CT scan, performed on a Cannon Aquilion Prime (Slice thickness [mm]: 0.8, Voxel size [mm3]: 0.564, 0.328, 0.527), which imaged the trunk of the body, from top of the abdomen to the bottom of the pelvis. The images were then used in Materialize Mimics Research 21.0 to create 3D images of individual organs, skin, fat, muscles, skeleton, and spinal cord. After pre-processing in Autodesk Meshmixer, the models were converted into solid CAD objects in Ansys SpaceClaim R2021 and combined into a single abdominal model. Ansys Maxwell R2021 was then used for simulations. Five different two-electrode configurations were tested in the prototype phase with a simplified model setup. The positive electrodes were placed over the (Thoracic) T10, T12, (Lumbar) L2 and L4 vertebrae sequentially, with the negative electrode over (Sacral) S2. The simulations took on average 47.4 hours. A marked decline in electrical current penetration depth was observed as the electrodes were placed closer together which was consistent with known current distribution patterns. A preliminary validation test was also performed using a lamb’s thigh. Two electrodes were placed a known distance apart and a stimulation was given, needle electrodes were then inserted in a grid-like pattern to obtain voltage values. The setup was recreated and simulated in Ansys Maxwell. The resulting average percent difference was 44.93 ± 33.3 % (5Vpp Square wave) and 35.02 ± 23.38 % (5V DC). In both instances, the highest difference was at the edges of the electrodes and the lowest difference in the midpoint between electrodes. Later versions of FEM models incorporated more organs and had improved on previous mesh generation flaws, but encountered new mesh generation errors which could not be rectified before the conclusion of the master’s project. Despite complications, this project has provided a pipeline for creating similar models and shown their usability. Future work will involve overcoming the current mesh generation errors, reducing calculation time, and performing a thorough validation test.

Association between the focus of attention and brain activation pattern during golf putting task in amateur and novice: A fNIRS Study

PurposeExternal focus of attention (FOA) has been shown to improve motor performance. However, recent research has found that the effectiveness of FOA is related to the level of expertise. Therefore, this study examined the effects of FOA on putting performance in golfers of different levels of expertise. The neural mechanisms behind FOA were explored in conjunction with fNIRS. MethodA total of 30 participants, including 15 amateurs (Mage: 23.31(SD = 1.32)years; 15 males) and 15 novices (Mage: 22.69(SD = 1.55) years; 11 males; 4 females) were recruited. Participants completed EF and IF golf putting at a duration of 3s per time wearing fNIRS for 3 blocks of 30 seconds interspersed with 10-second rest blocks. ResultBehavioral results showed a significant difference in the putting performance of the amateur group under the EF condition compared to the IF condition (P = 0.019), and relative to novices, the amateur group performed better under the EF condition (P = 0.003). fNIRS results revealed that the amateur group had higher activation levels in the right somatosensory association cortex (RSAC) and right motor cortex (RMC) under the IF condition. In contrast, for the novice group, higher activation levels were observed in the left prefrontal cortex and RMC under the EF condition. ConclusionsOur results revealed SAC and MC over-activation in the amateur group under IF conditions with poor golf putting performance. Our findings suggest that the impairment of automated motor neural networks could be a possible mechanism by which IF affects motor performance with SAC and MC over-activation. Guiding novices to focus on task-related factors consciously could be a potential mechanism by which EF enhances motor performance.

Photobiomodulation reduces spinal cord edema by decreasing the expression of AQP4 in the astrocytes of male spinal cord injury rats via the JAK2/STAT3 signaling pathway.

BackgroundSpinal cord swelling commonly occurs following SCI. Previous studies suggest that PBM may reduce inflammation and scar formation after SCI. However, whether PBM can alleviate post-spinal cord injury edema and its underlying mechanisms have not yet been reported. This study aims to investigate the effects of PBM on spinal cord swelling in rats following SCI and explore the underlying mechanisms. MethodsA rat model of SCI was established, and the rats received continuous PBM therapy for two weeks. Tissue hydration, motor function, AQP4 expression, and pathological changes in the spinal cord were evaluated at different time points. In vitro, astrocytes were subjected to PBM and treated with either cucurbitacin I or TGN020 following OGD. ResultsThe results indicate that PBM reduces tissue swelling in rats with SCI, improves motor function recovery, and inhibits the upregulation of AQP4 and GFAP associated with SCI. In vitro, PBM reduces abnormal activation of the JAK2/STAT3 signaling pathway in astrocytes, leading to decreased AQP4 synthesis and astrocyte activation. ConclusionsThese findings suggest that PBM reduces spinal cord swelling in rats after injury. This effect is associated with the inhibition of JAK2/STAT3 signaling pathway activation in astrocytes and the reduction in AQP4 expression.

Neuroprotective Effect of Echinoside on MPTP-induced Parkinson's Disease Mouse Model by Activation of NRF2/HO-1 Pathway

Echinacoside, a principal active compound derived from Cistanche deserticola Ma, is recognized in traditional Chinese medicine for its anti-aging, immunomodulatory, endocrine-regulating, and neuroprotective properties. However, the specific neuroprotective mechanisms of echinacoside remain largely unclear. This study aims to investigate whether the neuroprotective effects of echinacoside in a mouse model of Parkinson's disease (PD) are mediated through the Nrf2/HO-1 signaling pathway by mitigating inflammatory responses.Mice were divided into four groups: control, model, positive control, and echinacoside-treated groups. PD mouse model was induced through intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) over the course of one week, followed by three weeks of oral administration of echinacoside. The results demonstrated that echinacoside significantly improved motor function impairments caused by MPTP in PD mice. Immunohistochemical analysis revealed that echinacoside enhanced the expression of tyrosine hydroxylase in the substantia nigra of PD mice. Furthermore, assays of inflammatory cytokines indicated that echinacoside effectively reduced the levels of IL-6 and TNF-α in brain tissues.Western blot analysis further confirmed that echinacoside intervention upregulated the expression of Nrf2 and HO-1 in the brain tissues of PD mice. These findings suggest that echinacoside exerts neuroprotective effects in the PD mouse model, likely through the activation of the Nrf2/HO-1 signaling pathway. Therefore, echinacoside may be considered a potential therapeutic strategy for the treatment of PD.

Efficacy and safety of gene therapy with onasemnogene abeparvovec in children with spinal muscular atrophy in the D-A-CH-region: a population-based observational study

Real-world data on gene addition therapy (GAT) with onasemnogene abeparvovec (OA), including all age groups and with or without symptoms of the disease before treatment are needed to provide families with evidence-based advice and realistic therapeutic goals. Aim of this study is therefore a population-based analysis of all patients with SMA treated with OA across Germany, Austria and Switzerland (D-A-CH). This observational study included individuals with Spinal Muscular Atrophy (SMA) treated with OA in 29 specialized neuromuscular centers in the D-A-CH-region. A standardized data set including WHO gross motor milestones, SMA validated motor assessments, need for nutritional and respiratory support, and adverse events was collected using the SMArtCARE registry and the Swiss-Reg-NMD. Outcome data were analyzed using a prespecified statistical analysis plan including potential predictors such as age at GAT, SMN2 copy number, past treatment, and symptom status. 343 individuals with SMA (46% male, 54% female) with a mean age at OA of 14.0 months (range 0-90, IQR 20.0 months) were included in the analysis. 79 (23%) patients were clinically presymptomatic at the time of treatment. 172 (50%) patients received SMN2 splice-modifying drugs prior to GAT (risdiplam: n=16, nusinersen: n=154, both: n=2). Functional motor improvement correlated with lower age at GAT, with the best motor outcome in those younger than 6 weeks, carrying 3 SMN2 copies, and being clinically presymptomatic at time of treatment. The likelihood of requiring ventilation or nutritional support showed a significantly increase with older age at the time of GAT and remained stable thereafter. Pre-treatment had no effect on disease trajectories. Liver-related adverse events occurred significantly less frequently up to 8 months of age. All other adverse events showed an even distribution across all age and weight groups. Overall, motor, respiratory, and nutritional outcome were dependent on timing of GAT and initial symptom status. It was best in presymptomatic children treated within the first six weeks of life, but functional motor scores also increased significantly after treatment in all age groups up to 24 months. Additionally, OA was best tolerated when administered at a young age. Our study therefore highlights the need for SMA newborn screening and immediate treatment to achieve the best possible benefit-risk ratio. The SMArtCARE and Swiss-Reg-NMD registries are funded by different sources (see acknowledgements).

Circadian Intervention Improves Parkinson’s Disease and May Slow Disease Progression: A Ten Year Retrospective Study

Background: The involvement of the circadian system in the etiology and treatment of Parkinson’s disease (PD) is becoming an increasingly important topic. The prodromal symptoms of PD include insomnia, fatigue, depression and sleep disturbance which herald the onset of the primary symptoms of bradykinesia, tremor and rigidity while robbing patients of their quality of life. Light treatment (LT) has been implemented for modifying circadian function in PD but few studies have examined its use in a protracted term that characterizes PD itself. Methods: The present exploratory study monitors the effect of LT over a 10 year course of PD in the context of ongoing circadian function. Results: Improvement in circadian based symptoms were seen soon after LT commenced and continued for the duration of the study. Improvement in motor function was more subtle and was not distinguishable until 1.2 years after commencing treatment. Improvement in most motor and prodromal symptoms remained in steady state for the duration of the study as long as patients were compliant with daily use. Conclusions: The sequence of improvement in prodromal symptoms and motor function seen here parallels the slow, incremental repair process mimicking the protracted degenerative sequelae of PD that extends over decades. This process also emulates the slow incremental improvement characterizing the reparative course seen with circadian symptoms in other disorders that improve with LT. Recent findings from epidemiological work suggest that early disruption of circadian rhythmicity is associated with increased risk of PD and the present findings are consistent with that hypothesis. It is concluded that intervening in circadian function with LT presents a minimally invasive method that is compatible with internal timing that slows the degenerative process of PD.

Motor imagery technique for motor recovery of hand among sub-acute stroke patient: A randomized controlled trial

Stroke is the second leading cause of death globally, with a rising prevalence in line with increasing life expectancy. Hemiparesis, affecting up to 85% of stroke survivors, leads to impaired arm and hand movement, reduced strength, and limited coordination, significantly affecting daily activities. Despite rehabilitation efforts, many stroke survivors face persistent functional limitations or permanent disabilities. Intensive rehabilitation is often costly and constrained by the limited number of therapy sessions available in many centers. Therefore, strategies to enhance functional recovery while minimizing resource use are crucial. One promising approach is motor imagery (MI), a cognitive rehearsal of physical actions aimed at improving motor function. MI has been shown to activate similar brain areas as actual movement, such as the premotor cortex and supplementary motor area. While evidence supports MI's potential for enhancing motor recovery, clinical guidelines remain insufficient. This study aims to evaluate the effectiveness of motor imagery for improving hand function in subacute stroke patients. The primary objective is to assess the impact of MI on motor recovery using the Chedoke Arm and Hand Activity Inventory over a 4-week period.

Sulfasalazine improves neuronal function in mice with ischemic stroke by inhibiting the STING/NF-κB pathway.

Inflammation plays an essential role in the pathological processes of ischemic stroke (IS). Sulfasalazine is used in clinical practice for the treatment of inflammatory diseases. This study investigated the effects of sulfasalazine in mice with IS and its underlying mechanisms. We employed an in vivo mice model of middle cerebral artery occlusion (MCAO)/reperfusion, investigating the impact of sulfasalazine on MCAO mice using tetrazolium chloride (TTC) staining, behavioral experiments, and pathological staining. Utilizing of network pharmacology methodologies, we speculated that the protective effect of sulfasalazine against IS may be related to inflammation. The effects of sulfasalazine on inflammation and polarization in oxygen-glucose deprivation/re-oxygenation (OGD/R)-induced BV2 cells were examined through immunofluorescence and PCR techniques. Additionally, the influence of sulfasalazine on the STING/NF-κB pathway was assessed using Western blot and immunofluorescence techniques. Sulfasalazine significantly reduced the infarct area in MCAO mice, restored cerebral blood flow, and improved motor function in the MCAO mice. Pathological staining results indicated that sulfasalazine can mitigate neuronal damage in the cerebral cortex of MCAO mice. Immunofluorescence and PCR testing showed that sulfasalazine promotes M1 to M2 polarization, and reduces inflammation in OGD/R-induced BV2 cells. Furthermore, the Western blot and immunofluorescence results both confirmed that sulfasalazine can inhibit the activation of the STING/NF-κB pathway. This study elucidated the potential therapeutic role of sulfasalazine in IS through its anti-inflammatory effects and modulation of STING/NF-κB pathway, offering novel insights into treatment strategies for IS.

Efficacy of repetitive transcranial magnetic stimulation combined with peripheral magnetic stimulation on movement symptom and exploration of the optimal population in Parkinson's disease: A randomized controlled trial.

This study explores the efficacy of repetitive transcranial magnetic stimulation (rTMS) and rTMS combined with repetitive peripheral magnetic stimulation (rPMS) (hereinafter referred to as rTMS + rPMS) on motor symptoms and quality of life in Parkinson's disease (PD), and explores whether there are differences between the two treatment methods; At the same time, analyze data from different subgroups to explore the influencing factors, in order to find the most suitable treatment group. Eighty patients with PD were randomly divided into rTMS and rTMS + rPMS groups and administered 10 Hz rTMS, and 10 Hz rTMS + 25 Hz rPMS, respectively, for 10 days. Before and after treatment, the PD Motor Function Rating Scale (UPDRS Part III, 10m Walk Timing Test, Stand Up Walk Test Evaluation Scale (TUG)) and PD Quality of Life Questionnaire (PDQ-39) were used to evaluate the motor symptoms and quality of life. After quantifying the treatment effect, a comparative analysis of the efficacy before and after treatment was conducted. Simultaneously, we divided the two treatment groups into different subgroups, compared the subgroups under the same treatment method, analyzed the relevant factors affecting the treatment method, and found the most suitable treatment group. (1) After rTMS or rTMS + rPMS, all scoring scales improved compared to those before treatment (P < .05). Compared to rTMS, rTMS + rPMS resulted in greater improvements in overall motor function (UPDRS III) and quality of life (PDQ-39) (P < .05). (2) Patients with rigidity-based type as the main type may be the most suitable for these two treatment methods (P < .05).(3) There was no significant difference in treatment efficiency between the two treatment methods for patients with PD at different disease stages, sexes, or treatment ages(P > .05). Both rTMS and rTMS + rPMS can improve movement symptoms and quality of life in patients with PD. rTMS + rPMS was more beneficial for improving the overall motor function. Patients with rigidity-based type as the main type may be the most suitable for these two treatment methods. The therapies work in all age groups, all gender and irrespective of the disease stage with varying levodopa equivalent daily doses as well.

Strength training attenuates neuropathic pain by Preventing dendritic Spine dysgenesis through Suppressing Rac1 and inflammation in experimental autoimmune encephalomyelitis

Chronic pain is a challenge and major health problem to basic science and clinical practice. Pain is one of the worst symptoms of multiple sclerosis (MS), which has a significant impact on their quality of life. Rac1 is an important intracellular signaling molecule involved in spinal dendritic spine pathology and activation of IL-1β and TNF-α that are associated with chronic neuropathic pain. As a result, targeting Rac1 presents a promising approach to managing neuropathic pain. Clinical studies have demonstrated that physical exercise is a non-pharmacological strategy that positively influences disease progression in individuals with MS, but underlying mechanism of exercise on Rac1- induced neuropathic pain is not well understood. This study examined the effects of a 4-week strength training on Rac1 expression, IL-1B, TNF-α, TGF-β1 levels, MDA concentrations, SOD activity, dendritic spine abnormalities in the dorsal horn of the spinal cord, as well as nociceptive behaviors (formalin test) and motor function (Rotarod test) during the chronic phase of experimental autoimmune encephalomyelitis (EAE). The findings indicated that strength training increased TGF-β1 expression and SOD activity while decreasing the expression of Rac1, IL-1β, TNF-α, and MDA and reducing dendritic spine dysgenesis in the dorsal horn of the spinal cord. We observed strength training effectively reduced nociceptive behaviors and improved motor function in mice with EAE. In summary, regular physical exercise may modulate neuropathic pain through inhibition of dendritic spine dysgenesis, inflammation and oxidative stress in the dorsal horn of the spinal cord.

Bihemispheric Transcranial Direct Current Stimulation over Primary Motor Cortex Potentiates Improvement of Neurological but not Upper Limb Motor Functions in Ischemic Stroke Patients Treated with Routine Physical Therapy: A Randomized, Double-Blind, Sham-Controlled Trial.

We investigated the therapeutic effect of transcranial direct current stimulation (tDCS) combined with routine physiotherapy on the neurological and upper limb motor function in ischemic stroke patients with hemiplegia. In a Randomized double-blind controlled trial study, 52 eligible stroke patients were assigned to real tDCS receiving bihemispheric electrical current with 1.5 mA for 30 minutes over the primary motor cortex, and sham tDCS with a current intensity of 0.5 mA for 30 seconds. Both groups received routine physiotherapy, 5 sessions per week for two weeks. The National Institute of Health Stroke Scale (NIHSS) and the Medical Research Council Scale for Muscle Strength were used to assess the neurological and upper limb motor functions, respectively. Both therapeutic approaches begot a significant improvement in upper limb motor function and neurological impairment at the last session of therapy and follow-up study. However, the treatment-induced neurological amelioration at the last session of therapy in real tDCS was significantly more than sham, especially in those identified as female and under 60 years old. A gender and age-specific protocol of real tDCS combined with routine physiotherapy might be beneficial to improve neurological impairment but not upper limb motor dysfunction after stroke.