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Background: Astrocytes have been demonstrated to undergo conversion into functional neurons, presenting a promising approach for stroke treatment. However, the development of small molecules capable of effectively inducing this cellular reprogramming remains a critical challenge., Methods: Initially, we introduced a glial cell marker gene, GFaABC1D, as the promoter within an adeno-associated virus vector overexpressing miR-124 into the motor cortex of an ischemia-reperfusion model in rats. Additionally, we administered NeuroD1 as a positive control. Lentiviral vectors overexpressing miR-124 were constructed and transfected into primary rat astrocytes. We assessed the cellular distribution of GFAP, DCX, and NeuN on days 7, 14, and 28, respectively., Results: In rats with ischemic stroke, miR-124-transduced glial cells exhibited positive staining for the immature neuron marker doublecortin (DCX) and the mature neuron marker NeuN after 4 weeks. In contrast, NeuroD1-overexpressing model rats only expressed NeuN, and the positive percentage was higher in co-transfection with miR-124 and NeuroD1. Overexpression of miR-124 effectively ameliorated neurological deficits and motor functional impairment in the model rats. In primary rat astrocytes transduced with miR-124, DCX was not observed after 7 days of transfection, but it appeared at 14 days, with the percentage further increasing to 44.6% at 28 days. Simultaneously, 15.1% of miR-124-transduced cells exhibited NeuN positivity, which was not detected at 7 and 14 days. In vitro, double fluorescence assays revealed that miR-124 targeted Dll4, and in vivo experiments confirmed that miR-124 inhibited the expression of Notch1 and DLL4., Conclusions: The overexpression of miR-124 in astrocytes demonstrates significant potential for improving neurological deficits following ischemic stroke by inhibiting DLL4 expression, and it may facilitate astrocyte-to-neuronal transformation., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Accumulated evidence has proven that both acupuncture and rehabilitation therapy are beneficial for stroke sequelae. However, there is no systematic review to identify the efficacy and safety of acupuncture combined with rehabilitation training for poststroke cognitive impairment (PSCI). Therefore, the aim of this study was to assess the efficacy and safety of acupuncture combined with rehabilitation therapy for patients with PSCI., Methods: We searched nine databases, including PubMed, Embase, Scopus, Web of Science, EBSCO, Cochrane Library, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), and Wan Fang, from their inception to September 2022. Randomized controlled trials (RCTs) examining the effect of acupuncture combined with rehabilitation on PSCI were included. The primary outcomes were the Mini-Mental State Examination (MMSE) score, Montreal Cognitive Assessment (MoCA) score, Modified Barthel Index (MBI) score, and Fugl-Meyer Assessment (FMA) score. The quality of the methodology was evaluated by Cochrane's risk of bias tool. Meta-analyses were performed by Revman 5.3 software., Results: A total of 18 RCTs involving 1654 patients were included. The overall methodological quality of the included studies was low. Pooled results demonstrated that acupuncture combined with rehabilitation could significantly improve the clinical efficacy of PSCI (OR=3.23, 95% CI: 2.13 to 4.89), MMSE score (MD= 2.85, 95% CI: 2.56 to 3.15), MoCA score (MD= 2.18, 95% CI: 1.38 to 2.97), MBI score (MD= 9.23, 95% CI: 5.62 to 12.84), and FMA score (MD=5.72, 95% CI: 3.48 to 7.96)., Conclusions: Acupuncture combined with rehabilitation may produce better outcomes than rehabilitation alone in the treatment of PSCI. However, the safety of combined interventions is still unclear. Therefore, research with more rigorous study designs and RCTs with larger sample sizes is still needed., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Background: Based on the theory of interhemispheric inhibition and the bimodal balance-recovery model in stroke, we explored the effects of excitation/inhibition (E/I) of parvalbumin (PV) neurons in the contralateral primary motor cortex (cM1) connecting the ipsilateral M1 (iM1) via the corpus callosum (cM1-CC-iM1) of ischemic stroke rats by optogenetic stimulation., Methods: We tested this by injecting anterograde and retrograde virus in rats with middle cerebral artery occlusion (MCAO), and evaluated the neurological scores, motor behavior, volume of cerebral infarction and the E/I balance of the bilateral M1 two weeks after employing optogenetic treatment., Results: We found that concentrations of Glu and GABA decreased and increased, respectively, in the iM1 of MCAO rats, and that the former increased in the cM1, suggesting E/I imbalance in bilateral M1 after ischemic stroke. Interestingly, optogenetic stimulation improved M1 E/I imbalance, as illustrated by the increase of Glu in the iM1 and the decrease of GABA in both iM1 and cM1, which were accompanied by an improvement in neurological deficit and motor dysfunction. In addition, we observed a reduced infarct volume, an increase in the expression of the NMDAR and AMPAR, and a decrease in GAD67 in the iM1 after intervention., Conclusions: Optogenetic modulation of PV neurons of the iM1-CC-cM1 improve E/I balance, leading to reduced neurological deficit and improved motor dysfunction following ischemic stroke in rats., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background and Purpose: This study investigates the effect of physical activity (PA) on cognition in patients with cerebrovascular disease and explored the maximum benefit of different PA characteristics. Methods: Databases, such as Pubmed, Web of Science, Embase, and Cochrane Library, were searched from their inception to May 31, 2021. Standardized mean difference (SMD) and 95% confidence intervals (CI s) were calculated to generate a forest plot. In addition, subgroup analysis, moderation analysis, and regression analysis were performed to explore the possible adjustment factors. Results: In total, 22 studies that met the criteria were included, demonstrating data from 1,601 participants. The results indicated that PA produced a positive effect on the global cognition for patients with cerebrovascular disease (SMD: 0.20 [95% CI : 0.12–0.27]), at the same time, PA training prominently improved executive function (SMD: 0.09 [95% CI : 0.00–0.17]) and working memory (SMD: 0.25 [95% CI : 0.10–0.40]). Furthermore, patients with baseline cognitive impairment received the greater benefit of PA on cognition (SMD: 0.24 [95% CI : 0.14–0.34]) than those without cognitive impairment before intervention (SMD: 0.15 [95% CI : 0.04–0.26]). For patients in the acute stage (≤ 3 months), PA did not rescue impairment dysfunction significantly (SMD: 0.08 [95% CI : −0.04–0.21]) and remarkable cognitive gains were detected in the chronic stage of participants (>3 months) (SMD: 0.25 [95% CI : 0.16–0.35]). Moderate intensity PA showed a larger pooled effect size (SMD: 0.23 [95% CI : 0.11–0.36]) than low intensity (SMD: −0.01 [95% CI : −0.44–0.43]) and high intensity (SMD: 0.16 [95% CI : 0.03–0.29]). However, the different types, duration, and frequency of PA resulted in no differences in the improvement of cognitive function. Further regression analysis demonstrated that the beneficial effects of PA on cognition are negatively correlated with age (p < 0.05). Conclusions: This study revealed that PA can prominently improve the cognitive ability in patients with cerebrovascular diseases and strengthened the evidence that PA held promise as a widely accessible and effective non-drug therapy for vascular cognitive impairment (VCI). [ABSTRACT FROM AUTHOR]

Background: Evidences indicate that exosomes-mediated delivery of microRNAs (miRNAs or miRs) is involved in the neurogenesis of stroke. This study was to investigate the role of exosomal miRNAs in non-drug therapy of electro-acupuncture (EA) regulating endogenous neural stem cells for stroke recovery. Methods: The model of focal cerebral ischemia and reperfusion in rats were established by middle cerebral artery occlusion (MCAO) and treated by EA. The exosomes were extracted from peri-ischemic striatum and identified by exosomal biomarkers, and detected differentially expressed miRNAs with microarray chip. Primary stem cells were cultured, and oxygen–glucose deprivation and reperfusion (OGD/R) was used to mimic vitro ischemic injury. Results: The levels of exosomal biomarkers TSG101 and CD81 were increased in peri-ischemic striatum after EA treatment, and we revealed 25 differentially expressed miRNAs in isolated exosomes, of which miR-146b was selected for further analysis, and demonstrated that EA increased miR-146b expression and its inhibitors could block the effects. Subsequently, we confirmed that EA upregulated miR-146b expression to promote neural stem cells differentiation into neurons in peri-ischemic striatum. In vitro , it was verified that OGD/R hindered neural stem cells differentiation, and miR-146b inhibitors furtherly suppressed its differentiation, simultaneously NeuroD1 was involved in neural stem cells differentiation into neurons. Moreover, in vivo we found EA promoted NeuroD1-mediated neural stem cells differentiation via miR-146b. In addition, EA also could improve neurological deficits through miR-146b after ischemic stroke. Conclusion: EA promotes the differentiation of endogenous neural stem cells via exosomal miR-146b to improve neurological injury after ischemic stroke. [ABSTRACT FROM AUTHOR]