Summary of best evidence for rehabilitation management of patients with motor dysfunction after stroke. / è„‘å’ä¸­è¿åŠ¨åŠŸèƒ½éšœç¢æ‚£è€ åº·å¤ç®¡ç†çš„æœ€ä½³è¯æ®æ€»ç»“.

OBJECTIVES: The rehabilitation work for patients with motor dysfunction after stroke is crucial. However, there is currently a lack of summarized evidence regarding the rehabilitation management of stroke patients in rehabilitation wards, communities, and at home. This study aims to compile relevant evidence on the rehabilitation management of patients with motor dysfunction after stroke, providing a reference for clinical and community health professionals to carry out rehabilitation interventions. METHODS: A systematic search was conducted in BMJ Best Practice, UpToDate, National Guidebook Clearinghouse, American Heart Association/American Stroke Association, Canadian Medical Association, National Institute for Health and Clinical Excellence, United States Department of Veterans Affairs/ Department of Defense, Registered Nurses Association of Ontario, JBI Evidence-Based Healthcare Center Database, The Cochrane Library, PubMed, Web of Science, Embase, CINAHL, CNKI, Wanfang Database, SinoMed, and other databases for all literature on the rehabilitation management of patients with motor dysfunction after stroke. This included clinical decision-making, guidelines, expert consensuses, recommended practices, systematic reviews, and evidence summaries, with the search period spanning from the establishment of each database to October 2023. Two researchers independently evaluated the quality of the literature. RESULTS: A total of twenty-one documents were included, consisting of 11 guidelines, 2 expert consensus, and 8 systematic reviews. Evidence was extracted and integrated from the included literature, summarizing forty-five pieces of evidence across nine areas: rehabilitation management model, rehabilitation institutions, rehabilitation teams, timing of rehabilitation interventions, rehabilitation assessment, rehabilitation programs, rehabilitation duration and frequency, rehabilitation intensity, and rehabilitation support These covered comprehensive rehabilitation management content for stroke patients in the early, subacute, and chronic phases. CONCLUSIONS: The best evidence summarized in this study for the rehabilitation management of patients with motor dysfunction after stroke is comprehensive and of high quality. It provides important guidance for clinical and community healthcare professionals in carrying out rehabilitation interventions. When applying the evidence, it is recommended to consider the current condition of the stroke patient, the extent of motor dysfunction, environmental factors, and the patient's preferences. Then, select the most appropriate rehabilitation plan, and adjust the type and intensity of training according to each patient's specific needs and preferences.

A multimodal MRI study of XNKQ acupuncture for limb dysfunction after ischemic stroke: a randomized controlled study protocol.

Introduction: Limb motor dysfunction is one of the challenges in rehabilitation after cerebral ischemic stroke (CIS) and greatly affects the quality of life of patients. This study aims to investigate the central mechanisms of the curative effect with multimodal magnetic resonance imaging (MRI), which will provide additional evidence to support the application of Xingnao Kaiqiao (XNKQ) acupuncture. Methods and analysis: This trial is a randomized controlled trial. Patients who meet the criteria will be recruited and randomly divided into 2 groups. One group will receive acupuncture treatment and another group will not receive acupuncture treatment. Both groups will receive conventional treatment. In addition, 20 healthy individuals will be recruited who will not receive any treatment. The total course of treatment is 14 days. The primary outcome is multimodal MRI analysis. For safety assessment, adverse events will be observed and recorded. Ethics and dissemination: The study involving human subjects was reviewed and approved by the Ethics Committee of IRB of The First Teaching Hospital of Tianjin University of TCM (TYLL2023[K]031). This study complied with the Declaration of Helsinki. Written informed consent about this study was provided by the participants. The results of this study will be published in a peer-reviewed journal. Clinical trial registration: Chinese Clinical Trial Registration Center (ChiCTR2300078315) https://www.chictr.org.cn/.

Motor dysfunction in Parkinson's patients: depression differences in a latent growth model.

Objective: This study aims to utilize latent growth model (LGM) to explore the developmental trajectory of motor dysfunction in Parkinson's disease (PD) patients and investigate the relationship between depression and motor dysfunction. Methods: Four-year follow-up data from 389 PD patients were collected through the Parkinson's Progression Marker Initiative (PPMI). Firstly, a univariate LGM was employed to examine the developmental trajectory of motor dysfunction in PD patients. Subsequently, depression levels were introduced as covariates into the model, and depression was further treated as a parallel growth latent variable to study the longitudinal relationship between motor dysfunction and depression. Results: In the trajectory analysis of motor dysfunction, the fit indices for the quadratic growth LGM model were χ2 = 7.419, df = 6, CFI = 0.998, TLI = 0.997, SRMR = 0.019, and RMSEA = 0.025, indicating that the growth trend of motor dysfunction follows a quadratic curve rather than a simple linear pattern. Introducing depression symptoms as time-varying covariates to explore their effect on motor dysfunction revealed significant positive correlations (ß = 0.383, p = 0.026; ß = 0.675, p < 0.001; ß = 0.385, p = 0.019; ß = 0.415, p = 0.014; ß = 0.614, p = 0.003), suggesting that as depression levels increase, motor dysfunction scores also increase. Treating depression as a parallel developmental process in the LGM, the regression coefficients for depression intercept on motor dysfunction intercept, depression slope on motor dysfunction slope, and depression quadratic factor on motor dysfunction quadratic factor were 0.448 (p = 0.046), 1.316 (p = 0.003), and 1.496 (p = 0.038), respectively. These significant regression coefficients indicate a complex relationship between depression and motor dysfunction, involving not only initial level associations but also growth trends over time and possible quadratic effects. Conclusion: This study indicates a quadratic growth trajectory for motor dysfunction in PD, suggesting a continuous increase in severity with a gradual deceleration in growth rate. The relationship between depression and motor dysfunction is complex, involving initial associations, evolving trends over time, and potential quadratic effects. Exacerbation of depressive symptoms may coincide with motor function deterioration.

The efficacy and safety of gene therapy approaches in Parkinson's disease: A systematic review.

BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the brain. Despite existing treatments, there remains an unmet need for therapies that can halt or reverse disease progression. Gene therapy has been tried and tested for a variety of illnesses, including PD. The goal of this systematic review is to assess gene therapy techniques' safety and effectiveness in PD clinical trials. METHODS: Online databases PubMed/Medline, and Cochrane were used to screen the studies for this systematic review. The risk of bias of the included studies was assessed using standard tools. RESULTS: Gene therapy can repair damaged dopaminergic neurons from the illness or deal with circuit anomalies in the basal ganglia connected to Parkinson's disease symptoms. Rather than only treating symptoms, this neuroprotective approach alters the illness itself. Medication for gene therapy is currently administered at the patient's bedside. It can hyperactivate specific brain circuits associated with motor dysfunction. PD therapies are developing quickly, and there aren't enough head-to-head trials evaluating the safety and effectiveness of available treatments. When choosing an advanced therapy, patient-specific factors should be considered in addition to the effectiveness and safety of each treatment option. CONCLUSION: In comparison to conventional therapies, gene therapy may be advantageous for PD. It may minimize side effects, relieve symptoms, and offer dependable dopamine replacement.

Neuroprotective effects of dantrolene in neurodegenerative disease: Role of inhibition of pathological inflammation.

Neurodegenerative diseases (NDs) refer to a group of diseases in which slow, continuous cell death is the main pathogenic event in the nervous system. Most NDs are characterized by cognitive dysfunction or progressive motor dysfunction. Treatments of NDs mainly target alleviating symptoms, and most NDs do not have disease-modifying drugs. The pathogenesis of NDs involves inflammation and apoptosis mediated by mitochondrial dysfunction. Dantrolene, approved by the US Food and Drug Administration, acts as a RyRs antagonist for the treatment of malignant hyperthermia, spasticity, neuroleptic syndrome, ecstasy intoxication and exertional heat stroke with tolerable side effects. Recently, dantrolene has also shown therapeutic effects in some NDs. Its neuroprotective mechanisms include the reduction of excitotoxicity, apoptosis and neuroinflammation. In summary, dantrolene can be considered as a potential therapeutic candidate for NDs.

Expanding the clinical phenotype and genetic spectrum of GEMIN5 disorders: Early-infantile developmental and epileptic encephalopathies.

BACKGROUND: Several biallelic truncating and missense variants of the gem nuclear organelle-associated protein 5 (GEMIN5) gene have been reported to cause neurodevelopmental disorders characterized by cerebellar atrophy, intellectual disability, and motor dysfunction. However, the association between biallelic GEMIN5 variants and early-infantile developmental and epileptic encephalopathies (EIDEEs) has not been reported. PURPOSE: This study aimed to expand the phenotypic spectrum of GEMIN5 and explore the correlations between epilepsy and molecular sub-regional locations. METHODS: We performed whole-exome sequencing in two patients with EIDEE with unexplained etiologies. The damaging effects of variants were predicted using multiple in silico tools and modeling. All reported patients with GEMIN5 pathogenic variants and detailed neurological phenotypes were analyzed to evaluate the genotype-phenotype relationship. RESULTS: Novel biallelic GEMIN5 variants were identified in two unrelated female patients with EIDEE, including a frameshift variant (Hg19, chr5:154284147-154284148delCT: NM_015465: c.2551_c.2552delCT: p.(Leu851fs*30)), a nonsense mutation (Hg19, chr5:154299603-154299603delTinsAGA: NM_015465: c.1523delTinsAGA: p.(Leu508*)), and two missense variants (Hg19, chr5:154282663T > A: NM_015465: c.2705T > A: p.(Leu902Gln) and Hg19, chr5:154281002C > G: NM_015465: c.2911C > G: p.(Gln971Glu)), which were inherited from asymptomatic parents and predicted to be damaging or probably damaging using in silico tools. Except p.Leu508*, all these mutations are located in tetratricopeptide repeat (TPR) domain. Our two female patients presented with seizures less than 1 month after birth, followed by clusters of spasms. Brain magnetic resonance imaging suggests dysgenesis of the corpus callosum and cerebellar hypoplasia. Video electroencephalogram showed suppression-bursts. Through a literature review, we found 5 published papers reporting 48 patients with biallelic variants in GEMIN5. Eight of 48 patients have epilepsy, and 5 patients started before 1 year old, which reminds us of the relevance between GEMIN5 variants and EIDEE. Further analysis of the 49 GEMIN5 variants in those 50 patients demonstrated that variants in TPR-like domain or RBS domain were more likely to be associated with epilepsy. CONCLUSIONS: We found novel biallelic variants of GEMIN5 in two individuals with EIDEE and expanded the clinical phenotypes of GEMIN5 variants. It is suggested that the GEMIN5 gene should be added to the EIDEE gene panel to aid in the clinical diagnosis of EIDEE and to help determine patient prognosis.

Electroacupuncture blocked motor dysfunction and gut barrier damage by modulating intestinal NLRP3 inflammasome in MPTP-induced Parkinson's disease mice.

Parkinson's disease (PD) is a neurodegenerative disorder commonly accompanied by gut dysfunction. EA has shown anti-inflammatory and neuroprotective effects. Here, we aim to explore whether EA can treat Parkinson's disease by restoring the intestinal barrier and modulating NLRP3 inflammasome. We applied 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to establish a PD mouse model and EA at the GV16, LR3, and ST36 for 12 consecutive days. The open-field test results indicated that EA alleviated depression and behavioral defects, upregulated the expressions of tyrosine hydroxylase (TH) and brain-derived neurotrophic factor (BDNF), and blocked the accumulation of α-synuclein (α-syn) in the midbrain. Moreover, EA blocked the damage to intestinal tissues of PD mice, indicative of suppressed NLRP3 inflammasome activation and increased gut barrier integrity. Notably, the antibiotic-treated mouse experiment validated that the gut microbiota was critical in alleviating PD dyskinesia and intestinal inflammation by EA. In conclusion, this study suggested that EA exhibited a protective effect against MPTP-induced PD by alleviating behavioral defects, reversing the block of motor dysfunction, and improving the gut barrier by modulating intestinal NLRP3 inflammasome. Above all, this study could provide novel insights into the pathogenesis and therapy of PD.

Nurr1 overexpression in the primary motor cortex alleviates motor dysfunction induced by intracerebral hemorrhage in the striatum in mice.

Hemorrhage-induced injury of the corticospinal tract (CST) in the internal capsule (IC) causes severe neurological dysfunction in both human patients and rodent models of intracerebral hemorrhage (ICH). A nuclear receptor Nurr1 (NR4A2) is known to exert anti-inflammatory and neuroprotective effects in several neurological disorders. Previously we showed that Nurr1 ligands prevented CST injury and alleviated neurological deficits after ICH in mice. To prove direct effect of Nurr1 on CST integrity, we examined the effect of Nurr1 overexpression in neurons of the primary motor cortex on pathological consequences of ICH in mice. ICH was induced by intrastriatal injection of collagenase type VII, where hematoma invaded into IC. Neuron-specific overexpression of Nurr1 was induced by microinjection of synapsin I promoter-driven adeno-associated virus (AAV) vector into the primary motor cortex. Nurr1 overexpression significantly alleviated motor dysfunction but showed only modest effect on sensorimotor dysfunction after ICH. Nurr1 overexpression also preserved axonal structures in IC, while having no effect on hematoma-associated inflammatory events, oxidative stress, and neuronal death in the striatum after ICH. Immunostaining revealed that Nurr1 overexpression increased the expression of Ret tyrosine kinase and phosphorylation of Akt and ERK1/2 in neurons in the motor cortex. Moreover, administration of Nurr1 ligands 1,1-bis(3'-indolyl)-1-(p-chlorophenyl)methane or amodiaquine increased phosphorylation levels of Akt and ERK1/2 as well as expression of glial cell line-derived neurotrophic factor and Ret genes in the cerebral cortex. These results suggest that the therapeutic effect of Nurr1 on striatal ICH is attributable to the preservation of CST by acting on cortical neurons.

(+)-Borneol Protects Dopaminergic Neuronal Loss in Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-Induced Parkinson's Disease Mice: A Study of Dopamine Level using In Vivo Brain Microdialysis.

Considerable research efforts have been directed toward the symptom relief of Parkinson's disease (PD) by attenuating dopamine (DA) depletion. One common feature of these existing therapies is their unavailability of preventing the neurodegenerative process of dopaminergic neurons. (+)-Borneol, a natural highly lipid-soluble bicyclic monoterpene, has been reported to regulate the levels of monoamine neurotransmitters in the central nervous system and exhibit neuroprotective effects. However, the effect of (+)-borneol on the dopaminergic neuronal loss of methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice is not defined. Herein, we first report that 30 mg/kg (+)-borneol significantly attenuated the motor deficits of PD mice, which benefits from markedly increasing the level of DA and decreasing the metabolic rate of DA in the striatum of conscious and freely moving mouse detected by ultraperformance liquid chromatography tandem mass spectrometry online combined with in vivo brain microdialysis sampling. It is worth noting that the enhanced level of DA by (+)-borneol was enabled by the reduction in loss of tyrosine hydroxylase-immunoreactive dopaminergic neurons in the substantia nigra and striatum and promotion of reserpine- or nomifensine-induced DA release in PD mice. Interestingly, (+)-borneol evidently inhibited the decreased expression levels of DA transporter (DAT) and vesicular monoamine transporter 2 (VMAT2) on the MPTP mouse model of PD. Moreover, (+)-borneol suppressed the neuroinflammation by inhibiting the production of IL-1ß, IL-6, and TNF-α and attenuated oxidative stress by decreasing the level of MDA and increasing the activities of SOD and GSH-px in PD mice. These findings demonstrate that (+)-borneol protects DA neurons by inhibiting neuroinflammation and oxidative stress. Further research work for the neuroprotection mechanism of (+)-borneol will focus on reactive oxygen species-mediated apoptosis. Therefore, (+)-borneol is a potential therapeutic candidate for retarding the neurodegenerative process of PD.

The application value and improved warning criterion of D-wave monitoring in intramedullary spinal cord tumor surgery.

BACKGROUND CONTEXT: The primary treatment method for intramedullary spinal cord tumor (IMSCT) is surgical resection, but this procedure carries a significant risk of neurological damage. Intraoperative neurophysiological monitoring (IONM) has become a necessary adjunctive tool for IMSCT resection. PURPOSE: The current study aimed to explore the application value of D-wave monitoring in IMSCT surgery, and tried to investigate a tailored criterion for its early warning. STUDY DESIGN: A retrospective clinical study. PATIENT SAMPLE: A retrospective analysis was conducted based on the data of patients who underwent IMSCT surgeries performed by the same neurosurgical team at our hospital. IONM was applied in all surgeries. According to inclusion and exclusion criteria, ultimately 90 patients were enrolled in the study. OUTCOME MEASURES: The McCormick Scale (MMS) was applied to assess the functional outcome through outpatient visits or telephone follow-up at one month and six months postoperatively. Patients with an MMS grade over II one month after surgery were considered to have newly developed postoperative motor dysfunction (PMD). If the MMS grade could be restored to I or II six months after surgery, it was defined as a short-term PMD. Otherwise, it was defined as a long-term PMD. METHODS: The predictive value of different IONM modalities, including somatosensory evoked potential (SEP), muscle motor evoked potential (MEP), and D-wave for PMD, was assessed with sensitivity, specificity, positive predictive value, negative predictive value, and subsequent logistic regression analysis. At last, the cut-off value of the D-wave amplitude reduction ratio for predicting PMD was obtained through the receiver operating characteristic (ROC) curve analysis. RESULTS: SEP showed the worst performance in predicting short-term and long-term PMD. Significant MEP changes were indicated as an independent predictive factor for short-term PMD (OR 5.062, 95% CI 1.947-13.166, p=.001), while D-wave changes were demonstrated as an independent predictor for long-term PMD (OR 339.433, 95% CI 11.337-10770.311, p=.001). The optimum cut-off value of the D-wave amplitude reduction ratio for predicting long-term PMD was 42.18%, with a sensitivity of 100% and a specificity of 93.8% (AUC=0.981, p<.001). CONCLUSIONS: D-wave monitoring showed extremely high specificity in predicting PMD compared to SEP and MEP monitoring. Moreover, the authors suggested that a D-wave amplitude reduction of over 40% during IMSCT surgery generally indicates long-term PMD for patients.

P-tau217 correlates with neurodegeneration in Alzheimer's disease, and targeting p-tau217 with immunotherapy ameliorates murine tauopathy.

Neuronal loss is the central issue in Alzheimer's disease (AD), yet no treatment developed so far can halt AD-associated neurodegeneration. Here, we developed a monoclonal antibody (mAb2A7) against 217 site-phosphorylated human tau (p-tau217) and observed that p-tau217 levels positively correlated with brain atrophy and cognitive impairment in AD patients. Intranasal administration efficiently delivered mAb2A7 into male PS19 tauopathic mouse brain with target engagement and reduced tau pathology/aggregation with little effect on total soluble tau. Further, mAb2A7 treatment blocked apoptosis-associated neuronal loss and brain atrophy, reversed cognitive deficits, and improved motor function in male tauopathic mice. Proteomic analysis revealed that mAb2A7 treatment reversed alterations mainly in proteins associated with synaptic functions observed in murine tauopathy and AD brain. An antibody (13G4) targeting total tau also attenuated tau-associated pathology and neurodegeneration but impaired the motor function of male tauopathic mice. These results implicate p-tau217 as a potential therapeutic target for AD-associated neurodegeneration.

Effect of MEP-oriented scalp acupuncture combined with transcranial magnetic stimulation on limb motor ability in patients with ischemic stroke hemiplegia. / MEPå®šä½ä¸‹å¤´é’ˆè”åˆç»é¢ ç£åˆºæ¿€å¯¹ç¼ºè¡€æ€§è„‘å’ä¸­åç˜«æ‚£è€ è‚¢ä½“è¿åŠ¨èƒ½åŠ›çš„å½±å“.

OBJECTIVES: To observe the effect of motor evoked potential (MEP)-oriented scalp acupuncture combined with transcranial magnetic stimulation (TMS) on limb motor ability in patients with ischemic stroke hemiplegia. METHODS: A total of 60 patients with ischemic stroke hemiplegia were randomized into an observation group and a control group, 30 cases in each one. In addition to the medication treatment of internal medicine and comprehensive training of hemiplegic limbs, MEP-oriented scalp acupuncture combined with TMS was applied in the observation group, conventional scalp acupuncture at bilateral anterior oblique line of parietal and temporal regions combined with TMS was applied in the control group. The treatment was given once a day, 5 days a week for 4 weeks totally in the two groups. Before and after treatment, the scores of Fugl-Meyer assessment (FMA), modified Ashworth scale (MAS) and modified Barthel index (MBI) were observed in the two groups. RESULTS: After treatment, the FMA and MBI scores were increased compared with those before treatment in the two groups (P<0.001), and the FMA and MBI scores in the observation group were higher than those in the control group (P<0.05). After treatment, the MAS scores of upper and lower limbs in the observation group were decreased compared with those before treatment (P<0.01, P<0.001), the MAS score of lower limb in the control group was decreased compared with that before treatment (P<0.05). CONCLUSIONS: MEP-oriented scalp acupuncture combined with TMS can effectively improve the limb motor ability, daily living ability and limb spasticity in patients with ischemic stroke hemiplegia.

AFM signal model for dysarthric speech classification using speech biomarkers.

Neurological disorders include various conditions affecting the brain, spinal cord, and nervous system which results in reduced performance in different organs and muscles throughout the human body. Dysarthia is a neurological disorder that significantly impairs an individual's ability to effectively communicate through speech. Individuals with dysarthria are characterized by muscle weakness that results in slow, slurred, and less intelligible speech production. An efficient identification of speech disorders at the beginning stages helps doctors suggest proper medications. The classification of dysarthric speech assumes a pivotal role as a diagnostic tool, enabling accurate differentiation between healthy speech patterns and those affected by dysarthria. Achieving a clear distinction between dysarthric speech and the speech of healthy individuals is made possible through the application of advanced machine learning techniques. In this work, we conducted feature extraction by utilizing the Amplitude and frequency modulated (AFM) signal model, resulting in the generation of a comprehensive array of unique features. A method involving Fourier-Bessel series expansion is employed to separate various components within a complex speech signal into distinct elements. Subsequently, the Discrete Energy Separation Algorithm is utilized to extract essential parameters, namely the Amplitude envelope and Instantaneous frequency, from each component within the speech signal. To ensure the robustness and applicability of our findings, we harnessed data from various sources, including TORGO, UA Speech, and Parkinson datasets. Furthermore, the classifier's performance was evaluated based on multiple measures such as the area under the curve, F1-Score, sensitivity, and accuracy, encompassing KNN, SVM, LDA, NB, and Boosted Tree. Our analyses resulted in classification accuracies ranging from 85 to 97.8% and the F1-score ranging between 0.90 and 0.97.

Weight-Drop Method for Inducing Closed Head Diffuse Traumatic Brain Injury.

Traumatic brain injury (TBI) is one of the foremost causes of disability and death globally. Prerequisites for successful therapy of disabilities associated with TBI involved improved knowledge of the neurobiology of TBI, measurement of quantitative changes in recovery dynamics brought about by therapy, and the translation of quantitative methodologies and techniques that were successful in tracking recovery in preclinical models to human TBI. Frequently used animal models of TBI in research and development include controlled cortical impact, fluid percussion injury, blast injury, penetrating blast brain injury, and weight-drop impact acceleration models. Preclinical models of TBI benefit from controlled injury settings and the best prospects for biometric quantification of injury and therapy-induced gradual recovery from disabilities. Impact acceleration closed head TBI paradigm causes diffuse TBI (DTBI) without substantial focal brain lesions in rats. DTBI is linked to a significant rate of death, morbidity, and long-term disability. DTBI is difficult to diagnose at the time of hospitalization with imaging techniques making it challenging to take prompt therapeutic action. The weight-drop method without craniotomy is an impact acceleration closed head DTBI model that is used to induce mild/moderate diffuse brain injuries in rodents. Additionally, we have characterized neuropathological and neurobehavioral outcomes of the weight-drop model without craniotomy for inducing closed head DTBI of graded severity with a range of mass of weights (50-450 gm). This chapter also discusses techniques and protocols for measuring numerous functional disabilities and pathological changes in the brain brought on by DTBI.

Constraint-Induced Movement Therapy Promotes Myelin Remodeling and Motor Function by Mediating Sox2/Fyn Signals in Rats With Hemiplegic Cerebral Palsy.

OBJECTIVE: Hypoxic-ischemic brain injury in infants often leads to hemiplegic motor dysfunction. The mechanism of their motor dysfunction has been attributed to deficiencies of the transcription factor sex-determining region (SRY) box 2 (Sox2) or the non-receptor-type tyrosine kinase Fyn (involved in neuronal signal transduction), which causes a defect in myelin formation. Constraint-induced movement therapy (CIMT) following cerebral hypoxia-ischemia may stimulate myelin growth by regulating Sox2/Fyn, Ras homolog protein family A (RhoA), and rho-associated kinase 2 (ROCK2) expression levels. This study investigated how Sox2/Fyn regulates myelin remodeling following CIMT to improve motor function in rats with hemiplegic cerebral palsy (HCP). METHODS: To investigate the mechanism of Sox2 involvement in myelin growth and neural function in rats with HCP, Lentivirus (Lenti)-Sox2 adeno-associated virus and negative control-Lenti-Sox2 (LS) adeno-associated virus were injected into the lateral ventricle. The rats were divided into a control group and an HCP group with different interventions (CIMT, LS, or negative control-LS [NS] treatment), yielding the HCP, HCP plus CIMT (HCP + CIMT), HCP + LS, HCP + LS + CIMT, HCP + NS, and HCP + NS + CIMT groups. Front-limb suspension and RotaRod tests, Golgi-Cox staining, transmission electron microscopy, immunofluorescence staining, western blotting, and quantitative polymerase chain reaction experiments were used to analyze the motor function, dendrite/axon area, myelin ultrastructure, and levels of expression of oligodendrocytes and Sox2/Fyn/RhoA/ROCK2 in the motor cortex. RESULTS: The rats in the HCP + LS + CIMT group had better values for motor function, dendrite/axon area, myelin ultrastructure, oligodendrocytes, and Sox2/Fyn/RhoA/ROCK2 expression in the motor cortex than rats in the HCP and HCP + NS groups. The improvement of motor function and myelin remodeling, the expression of oligodendrocytes, and the expression of Sox2/Fyn/RhoA/ROCK2 in the HCP + LS group were similar to those in the HCP + CIMT group. CONCLUSION: CIMT might overcome RhoA/ROCK2 signaling by upregulating the transcription of Sox2 to Fyn in the brain to induce the maturation and differentiation of oligodendrocytes, thereby promoting myelin remodeling and improving motor function in rats with HCP. IMPACT: The pathway mediated by Sox2/Fyn could be a promising therapeutic target for HCP.

Efficacy of therapy by MK-28 PERK activation in the Huntington's disease R6/2 mouse model.

There is currently no disease-modifying therapy for Huntington's disease (HD). We recently described a small molecule, MK-28, which restored homeostasis in HD models by specifically activating PKR-like ER kinase (PERK). This activation boosts the unfolded protein response (UPR), thereby reducing endoplasmic reticulum (ER) stress, a central cytotoxic mechanism in HD and other neurodegenerative diseases. Here, we have tested the long-term effects of MK-28 in HD model mice. R6/2 CAG (160) mice were treated by lifetime intraperitoneal injections 3 times a week. CatWalk measurements of motor function showed strong improvement compared to untreated mice after only two weeks of MK-28 treatment and continued with time, most significantly at 1 â€‹mg/kg MK-28, approaching WT values. Seven weeks treatment significantly improved paw grip strength. Body weight recovered and glucose levels, which are elevated in HD mice, were significantly reduced. Treatment with another PERK activator, CCT020312 at 1 â€‹mg/kg, also caused amelioration, consistent with PERK activation. Lifespan, measured in more resilient R6/2 CAG (120) mice with daily IP injection, was much extended by 16 days (20%) with 0.3 â€‹mg/kg MK-28, and by 38 days (46%) with 1 â€‹mg/kg MK-28. No toxicity, measured by weight, blood glucose levels and blood liver function markers, was detectable in WT mice treated for 6 weeks with 6 â€‹mg/kg MK-28. Boosting of PERK activity by long-term treatment with MK-28 could be a safe and promising therapeutic approach for HD.

Neuroprotective effects of levothyroxine on cognition deficits and memory in an experimental model of Huntington's disease in rats: An electrophysiological study.

Huntington's disease (HD) is a neurodegenerative disorder characterized by cognitive deficits and motor function. Levothyroxine (L-T4) is a synthetic form of Thyroxine (T4), which can improve cognitive ability. The aim of the present study was to determine the neuroprotective effect of L-T4 administration in rats with 3-nitropropionic acid (3-NP)-induced Huntington's disease. Forty-eight Wistar male rats were divided into six groups (n = 8): Group 1 control group that received physiological saline, Group 2 and 3: which received L-T4 (30 and 100 µg/kg), Group 4: HD group that received 3-NP and Groups 5 and 6: The treatment of the HD rats with L-T4 (30 and 100 µg/kg). Spatial memory, locomotor activity, and frequency of neuronal firing were assessed. After decapitation, the Brain-Derived Neurotrophic Factor (BDNF) and Total antioxidant capacity (TAC) levels in the striatum was measured. The results showed that the indices of spatial memory (mean path length and latency time) and motor dysfunction (immobility time) significantly increased, while time spent in the goal quadrant, swimming speed, spike rate, and striatum levels of BDNF significantly decreased in the HD group compared to the control group. L-T4 treatment significantly enhanced time spent in the goal quadrant, swimming speed, motor activity (number of line crossing and rearing), spike rate and striatal BDNF level. This research showed that L-T4 prevented the disruption of motor activity and cognitive deficiencies induced by 3-NP. The beneficial effects of L-T4 may be due to an increase in the concentration of BDNF and enhancement of the spike rate in the striatum.

Slow-wave sleep and REM sleep without atonia predict motor progression in Parkinson's disease.

BACKGROUND: Growing evidence supports the potential role of sleep in the motor progression of Parkinson's disease (PD). Slow-wave sleep (SWS) and rapid eye movement (REM) sleep without atonia (RWA) are important sleep parameters. The association between SWS and RWA with PD motor progression and their predictive value have not yet been elucidated. METHODS: We retro-prospectively analyzed clinical and polysomnographic data of 136 patients with PD. The motor symptoms were assessed using Unified Parkinson's Disease Rating Scale Part III (UPDRS III) at baseline and follow-up to determine its progression. Partial correlation analysis was used to explore the cross-sectional associations between slow-wave energy (SWE), RWA and clinical symptoms. Longitudinal analyses were performed using Cox regression and linear mixed-effects models. RESULTS: Among 136 PD participants, cross-sectional partial correlation analysis showed SWE decreased with the prolongation of the disease course (P = 0.046), RWA density was positively correlated with Hoehn & Yahr (H-Y) stage (tonic RWA, P < 0.001; phasic RWA, P = 0.002). Cox regression analysis confirmed that low SWE (HR = 1.739, 95% CI = 1.038-2.914; P = 0.036; FDR-P = 0.036) and high tonic RWA (HR = 0.575, 95% CI = 0.343-0.963; P = 0.032; FDR-P = 0.036) were predictors of motor symptom progression. Furthermore, we found that lower SWE predicted faster rate of axial motor progression (P < 0.001; FDR-P < 0.001) while higher tonic RWA density was associated with faster rate of rigidity progression (P = 0.006; FDR-P = 0.024) using linear mixed-effects models. CONCLUSIONS: These findings suggest that SWS and RWA might represent markers of different motor subtypes progression in PD.

Interactive scalp acupuncture combined with suspension digital occupational therapy for upper limb motor dysfunction after stroke: a multi-center randomized controlled trial. / äº’åŠ¨å¼å¤´é’ˆç»“åˆæ‚¬åŠä¸‹æ•°å­—ä½œä¸šç–—æ³•æ²»ç–—è„‘å’ä¸­åŽä¸Šè‚¢è¿åŠ¨åŠŸèƒ½éšœç¢ï¼šå¤šä¸­å¿ƒéšæœºå¯¹ç §è¯•éªŒ.

OBJECTIVES: To observe the effects of interactive scalp acupuncture on upper limb motor function and activities of daily living in patients with upper limb motor dysfunction after stroke. METHODS: One hundred and twenty patients with upper limb motor dysfunction after stroke were randomly divided into an observation group(60 cases, 2 cases dropped out)and a control group(60 cases, 1 case dropped out). Both groups were treated with routine medication and rehabilitation. The observation group was treated with interactive scalp acupuncture combined with suspension digital occupational therapy, interactive scalp acupuncture was applied at middle 2/5 of the parietal and temporal anterior oblique line, middle 2/5 of the parietal and temporal posterior oblique line and second lateral line of parietal of the hemiparalysis contralateral side, 30 min each time.The control group was treated with suspension digital occupational therapy alone. The treatment was given once a day, 5 times a week for 4 weeks in the two groups. The scores of Fugl-Meyer assessment scale of upper extremity(FMA-UE), action research arm test(ARAT), the modified Barthel index (MBI) and surface electromyography(sEMG)signal of the biceps and triceps on the affected side were observed before and after treatment in the two groups, and the clinical efficacy was evaluated. RESULTS: After treatment, the FMA-UE, ARAT and MBI scores were increased compared with those before treatment in both groups(P<0.05), the changes of the observation group were greater than those in the control group(P<0.05). After treatment, the integrated electromyography(iEMG)value and root mean square(RMS)value of the biceps and triceps on the affected side during elbow flexion and extension were increased compared with those before treatment in both groups(P<0.05), the changes of the observation group were greater than those in the control group(P<0.05). The total effective rate was 94.8%(55/58) in the observation group, which was higher than 83.1%(49/59) in the control group(P<0.05). CONCLUSIONS: Interactive scalp acupuncture could improve upper limb motor function and activities of daily living in patients with upper limb motor dysfunction after stroke.

The Association between Intracranial Calcifications and Symptoms in Patients with Primary Familial Brain Calcification.

(1) Background: Primary Familial Brain Calcification (PFBC) is a neurodegenerative disease characterized by bilateral calcifications of the basal ganglia and other intracranial areas. Many patients experience symptoms of motor dysfunction and cognitive disorders. The aim of this study was to investigate the association between the amount and location of intracranial calcifications with these symptoms. (2) Methods: Patients with suspected PFBC referred to our outpatient clinic underwent a clinical work-up. Intracranial calcifications were visualized on Computed Tomography (CT), and a Total Calcification Score (TCS) was constructed. Logistic and linear regression models were performed. (3) Results: Fifty patients with PFBC were included in this study (median age 64.0 years, 50% women). Of the forty-one symptomatic patients (82.0%), 78.8% showed motor dysfunction, and 70.7% showed cognitive disorders. In multivariate analysis, the TCS was associated with bradykinesia/hypokinesia (OR 1.07, 95%-CI 1.02-1.12, p < 0.01), gait ataxia (OR 1.06, 95%-CI 1.00-1.12, p = 0.04), increased fall risk (OR 1.04, 95%-CI 1.00-1.08, p = 0.03), and attention/processing speed disorders (OR 1.06, 95%-CI 1.01-1.12, p = 0.02). Calcifications of the lentiform nucleus and subcortical white matter were associated with motor and cognitive disorders. (4) Conclusions: cognitive and motor symptoms are common among patients with PFBC, and there is an association between intracranial calcifications and these symptoms.