Ischemic stroke (IS) remains one of the most serious threats to human life. Early blood-brain barrier damage (BBB) is the cause of parenchymal cell damage. Repair of the structure and function of the BBB is beneficial for the treatment of IS. The traditional prescription ginseng aconitum decoction (GAD) has a long history in the treatment of cardiovascular and cerebrovascular diseases, however, the effect of GAD on the BBB disruption and underlying mechanisms remains largely unknown. To address these issues, in vitro models of BBB were established with brain endothelial cells (bEnd.3). We found that GAD reduced the leakage of the fluorescent probe FITC-dextran (P < 0.01) and increased the expression of tight junction proteins (Claudin-5, ZO-1) (P < 0.05) in the BBB model in vitro. Furthermore, to investigate the BBB protective effects of GAD in vivo. A total of 25 male C57/BL6 mice (20-22 g) were randomly divided into 5 groups (n = 5 per group): (1) Sham group (saline), (2) MCAO group (saline), (3) MCAO + CG group (Chinese ginseng 8 mg/kg/day), (4) MCAO + AC group (aconite 8 mg/kg/day), (5) MCAO + GAD group (GAD 8 mg/kg/day).We constructed IS model in mice and found that GAD treatment reduced IgG leakage (P < 0.05), up-regulated the expression of tight junction proteins Claudin-5, Occludin, and ZO-1 (P < 0.05). Further mechanism study showed that fatty acid oxidation (FAO) of vascular endothelial cells is involved in the protection of the BBB after cerebral IS, and GAD regulates FAO (P < 0.05) to protect BBB. In addition, we found the effect of GAD was stronger than that of Chinese ginseng (CG) (P < 0.05) and aconite (AC) (P < 0.01) alone. We concluded that GAD ameliorated the BBB dysfunction by regulating FAO involving vascular endothelial cells after IS. At the same time, the prescription is more effective than single traditional Chinese medicine.

After ischemic stroke (IS), secondary injury is intimately linked to endoplasmic reticulum (ER) stress and body-brain crosstalk. Nonetheless, the underlying mechanism systemic immune disorder mediated ER stress in human IS remains unknown. In this study, 32 candidate ER stress-related genes (ERSRGs) were identified by overlapping MSigDB ER stress pathway genes and DEGs. Three Key ERSRGs (ATF6, DDIT3 and ERP29) were identified using LASSO, random forest, and SVM-RFE. IS patients with different ERSRGs profile were clustered into two groups using consensus clustering and the difference between 2 group was further explored by GSVA. Through immune cell infiltration deconvolution analysis, and middle cerebral artery occlusion (MCAO) mouse scRNA analysis, we found that the expression of 3 key ERSRGs were closely related with peripheral macrophage cell ER stress in IS and this was further confirmed by RT-qPCR experiment. These ERS genes might be helpful to further accurately regulate the central nervous system and systemic immune response through ER stress and have potential application value in clinical practice in IS.

OBJECTIVE: The purpose of this study was to evaluate the effectiveness of Governor vessel acupuncture (GV Ac) in treating post-stroke cognitive impairment (PSCI).
METHODS: There was a total of seven databases examined. Four English databases (Cochrane Library, PubMed, Embase, and Medline) and three Chinese databases (Chinese National Knowledge Infrastructure (CNKI), Chinese Science and Technology Periodical Databases (VIP), and Wan Fang Database) contain all randomized controlled trials (RCTs) comparing Governor vessel acupuncture to other treatments or none acupuncture for PSCI. The exact dates for the search period are from January 1, 2000, to January 1, 2023.Two researchers independently reviewed the literature, gathered RCT data, and performed statistical analysis. All data were analyzed using Review Manager software (Rev Man) 5.3.
RESULTS: This meta-analysis includes a total of 39 trials with 2044 patients. There were 1022 participants in each of the test and control groups. Following 12-120 days of acupuncture treatment, a meta-analysis revealed that the treatment groups (GV Ac combined with conventional treatment groups) significantly increased their scores on the Curative ratio (OR=3.00, 95%CI=2.37-3.79, P=0.98, I²=0%), Montreal Cognitive Assessment (MoCA)(MD=1.82, 95%CI=1.60-2.03, P=0.11, I²=25%), Mini-Mental State Examination (MMSE)(MD=2.18, 95%CI=1.64-2.72, P<0.005, I²=92%), and Activity of Daily Living (ADL)(MD=5.99, 95%CI=5.33-6.64, P=0.19, I²=26%).
CONCLUSIONS: The results suggested that acupuncture on points of the Governor vessel enhanced cognitive function in stroke survivors.

BACKGROUND: Dyskinesia is one of the most common complications of stroke. Acupuncture therapy (AT) and mirror therapy (MT) are promising rehabilitation measures for the treatment of post-stroke dyskinesia. Although some studies suggested that AT and MT are effective and safe for dyskinesia, the effects, and safety remain uncertain due to lacking strong evidence. The purpose of this study is to investigate the efficacy and safety of AT combined with MT in the treatment of post-stroke dyskinesia.
METHODS: We searched the following databases: PubMed, Web of Science, Cochrane Library, EMBASE, Medline, China Knowledge Network, WANFANG, and China Biomedical Literature Database, from inception to 1 January 2023 to identify eligible studies. Total effective rate, the Fugl-Meyer assessment scale (FMA) upper and lower limb scores, modified Barthel index scores, Berg balance scale, modified Ashworth scale, and adverse reactions were adopted as outcome indicators. The Grading of Recommendations Assessment Development and Evaluation system was used by 2 independent reviewers to assess the quality of evidence for the outcome indicators included in the study. The statistical analysis was conducted by RevMan V.5.4 software.
RESULTS: A total of 24 randomized controlled studies included 2133 patients with post-stroke dyskinesia were included. The total effective rate of AT combined with MT was more advantageous in the treatment of post-stroke dyskinesia (relative risk = 1.31, 95% confidence interval [CI] [1.22-1.42], Z = 6.96, P < .0001). AT combined with MT was more advantageous for FMA upper limb score (mean difference [MD] = 6.67, 95% CI [5.21-8.13], Z = 8.97, P < .00001) and FMA lower limb score (MD = 3.72, 95% CI [2.81-4.63], Z = 7.98, P < .00001). Meta-analysis showed that AT combined with MT for post-stroke dyskinesia had a more advantageous modified Barthel index score (MD = 9.51, 95% CI [7.44-11.58], Z = 9.01, P < .00001).
CONCLUSIONS: AT combined with MT is effective in improving motor function and daily living ability of patients, especially in improving muscle spasms. However, these results should be regarded with caution given the low quality of evidence for the evaluation results.

BACKGROUND: Home-based rehabilitation is a cost-effective means of making services available for patients. The aim of this study is to determine the evidence in the literature on the effects of home-based neurostimulation in patients with stroke.
METHODS: We searched PubMED, Embase, Web of Science, Scopus, and CENTRAL for randomized controlled trials on the subject matter using keywords such as stroke, electrical stimulation and transcranial direct current stimulation. Information on participants\' characteristics and mean scores on the outcomes of interest were extracted. Risks of bias and methodological quality of the included studies were assessed using Cochrane Risks of bias tool and PEDro scale respectively. The data was analyzed using both narrative and quantitative syntheses. In the quantitative synthesis, meta-analysis was carried out using random effect model analysis.
RESULTS: The results showed that, home-based neurostimulation is superior to the control at improving upper limb muscle strength (SMD = 0.72, 95% CI = 0.08 to 1.32, p = 0.03), functional mobility (SMD = -0.39, 95% CI = -0.65 to 0.14, p = 0.003) and walking endurance (SMD = 0.33, 95% CI = 0.08 to 0.59, p = 0.01) post intervention; and upper limb motor function (SMD = 0.9, 95% CI = 0.10 to 1.70, p = 0.03), functional mobility (SMD = -0.30, 95% CI = -0.56 to -0.05, p = 0.02) and walking endurance (SMD = 0.33, 95% CI = 0.08 to 0.59, p = 0.01) at follow-up.
CONCLUSIONS: Home-based neurostimulation can be used to improve upper and lower limb function after stroke.

Histone deacetylase 9 (HDAC9) is implicated in ischemic stroke by genome-wide association studies. We conducted a series of experiments using a mouse model of ischemic stroke (middle cerebral artery occlusion followed by reperfusion) to examine the potential role of HDAC9. Briefly, HDAC9 was upregulated in the penumbra. Deletion of HDAC9 from neurons reduced infarction volume, inhibited neuronal apoptosis in the penumbra, and improved neurological outcomes. HDAC9 knockout from neurons in the penumbra upregulated cGMP-dependent kinase II (cGK II), blocking which abrogated the protective effects of HDAC9 deletion. Mechanistically, HDAC9 interacts with the transcription factor MEF2, thereby inhibiting MEF2\'s binding to the promoter region of the cGK II gene, which results in the suppression of cGK II expression. Inhibiting the interaction between HDAC9 and MEF2 by BML210 upregulated cGK II and attenuated ischemic injury in mice. These results encourage targeting the HDAC9-MEF2 interaction in developing novel therapy against ischemic stroke.

OBJECTIVE: Family resilience and healthy family functioning are crucial for stroke survivors\' rehabilitation. This study aimed to determine the mediating effects of self-efficacy and confrontation coping on the relationship between family resilience and functioning among patients with first-episode stroke.
METHODS: A cross-sectional design was applied.
METHODS: 288 patients with first-episode stroke were recruited from 7 hospitals in Shangqiu and Shanghai, China, from July 2020 to October 2020. A shortened Chinese version of the Family Resilience Assessment Scale, family adaptation, partnership, growth, affection and resolve questionnaire, Medical Coping Modes Questionnaire, and Self-efficacy for Chronic Disease 6-item Scale were used to collect the self-reported data. The relationships among the studied variables were studied using spearman correlation and structural equation model.
RESULTS: The average level of family functioning among stroke patients was 7.87 (SD = 2.32). About 26.8% (n = 76) of patients reported family dysfunction. The structural equation model showed that family resilience directly affected patients\' satisfaction with family functioning (r = 0.406, p < 0.001) and indirectly affected the mediating role of patients\' self-efficacy and confrontation coping style (r = 0.119, p < 0.001). The model was with good fit (χ2/df = 2.128, RMSEA = 0.065, GFI = 0.956, AGFI = 0.919, NFI = 0.949, and TLI = 0.956).
CONCLUSIONS: Family resilience and functioning among patients with first-episode stroke are positively associated with the mediating effects of the patients\' confrontation coping style and self-efficacy between family resilience and functioning. The findings indicate that the professionals should pay special attention to families exhibiting poor family resilience or with patients who rarely use confrontation coping styles or with poor self-efficacy since they are more likely to suffer from low functioning.

Elevated levels of blood glucose in patients with ischemic stroke are associated with a worse prognosis. The present study aimed to explore whether hyperglycemia promotes microglial pyroptosis by increasing the oxygen extraction rate in an acute ischemic stroke model. C57BL/6 mice that underwent middle cerebral artery occlusion were used for assessment of blood glucose level and neurological function. The cerebral oxygen extraction ratio (CERO2), oxygen consumption rate (OCR) and partial pressure of brain tissue oxygen (PbtO2) were measured. To investigate the significance of the NOD‑like receptor protein 3 (NLRP3) inflammasome, NLRP3‑/‑ mice were used, and the expression levels of NLRP3, caspase‑1, full‑length gasdermin D (GSDMD‑FL), GSDMD‑N domain (GSDMD‑N), IL‑1β and IL‑18 were evaluated. In addition, Z‑YVAD‑FMK, a caspase‑1 inhibitor, was used to treat microglia to determine whether activation of the NLRP3 inflammasome was required for the enhancing effect of hyperglycemia on pyroptosis. It was revealed that hyperglycemia accelerated cerebral injury in the acute ischemic stroke model, as evidenced by decreased latency to fall and the percentage of foot fault. Hyperglycemia aggravated hypoxia by increasing the oxygen extraction rate, as evidenced by increased CERO2 and OCR, and decreased PbtO2 in response to high glucose treatment. Furthermore, hyperglycemia‑induced microglial pyroptosis was confirmed by detection of increased levels of caspase‑1, GSDMD‑N, IL‑1β and IL‑18 and a decreased level of GSDMD‑FL. However, the knockout of NLRP3 attenuated these effects. Pharmacological inhibition of caspase‑1 also reduced the expression levels of GSDMD‑N, IL‑1β and IL‑18 in microglial cells. These results suggested that hyperglycemia stimulated NLRP3 inflammasome activation by increasing the oxygen extraction rate, thus leading to the aggravation of pyroptosis following ischemic stroke.

The human central nervous system (CNS) has a limited capacity for regeneration and repair, as many other organs do. Partly as a result, neurological diseases are the leading cause of medical burden globally. Most neurological disorders cannot be cured, and primary treatments focus on managing their symptoms and slowing down their progression. Cell therapy for neurological disorders offers several therapeutic potentials and provides hope for many patients. Here we provide a general overview of cell therapy in neurological disorders such as Parkinson\'s disease (PD), Alzheimer\'s disease (AD), amyotrophic lateral sclerosis (ALS), Wilson\'s disease (WD), stroke and traumatic brain injury (TBI), involving many forms of stem cells, including embryonic stem cells and induced pluripotent stem cells. We also address the current concerns and perspectives for the future. Most studies for cell therapy in neurological diseases are in the pre-clinical stage, and there is still a great need for further research to translate neural replacement and regenerative therapies into clinical settings.

UNASSIGNED: Upwards of 50% of acute ischemic stroke (AIS) survivors endure varying degrees of disability, with a recurrence rate of 17.7%. Thus, the prediction of outcomes in AIS may be useful for treatment decisions. This study aimed to determine the applicability of a machine learning approach for forecasting early outcomes in AIS patients.
UNASSIGNED: A total of 659 patients with new-onset AIS admitted to the Department of Neurology of both the First and Second Affiliated Hospitals of Bengbu Medical University from January 2020 to October 2022 included in the study. The patient\' demographic information, medical history, Trial of Org 10,172 in Acute Stroke Treatment (TOAST), National Institute of Health Stroke Scale (NIHSS) and laboratory indicators at 24 h of admission data were collected. The Modified Rankine Scale (mRS) was used to assess the 3-mouth outcome of participants\' prognosis. We constructed nine machine learning models based on 18 parameters and compared their accuracies for outcome variables.
UNASSIGNED: Feature selection through the Least Absolute Shrinkage and Selection Operator cross-validation (Lasso CV) method identified the most critical predictors for early prognosis in AIS patients as white blood cell (WBC), homocysteine (HCY), D-Dimer, baseline NIHSS, fibrinogen degradation product (FDP), and glucose (GLU). Among the nine machine learning models evaluated, the Random Forest model exhibited superior performance in the test set, achieving an Area Under the Curve (AUC) of 0.852, an accuracy rate of 0.818, a sensitivity of 0.654, a specificity of 0.945, and a recall rate of 0.900.
UNASSIGNED: These findings indicate that RF models utilizing general clinical and laboratory data from the initial 24 h of admission can effectively predict the early prognosis of AIS patients.