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Background/Aim: Evidence suggests that gut microbiota can affect various neurological diseases, including stroke. Stroke patients have an increase in harmful gut bacteria and a decrease in beneficial bacteria. This increases intestinal permeability, increases the risk of infection, and even affects many inflammatory factors. While probiotics may affect stroke prognosis by improving the gut environment. This study aimed to investigate the effect of probiotic Bifico on the neural function in mice after focal cerebral ischemia and explore its mechanisms of action. Materials and Methods: A focal cerebral ischemia model was established in mice. Four weeks before modeling, animals were divided into three groups: Stroke plus Vehicle group, Stroke plus Pre-Bifico group and Bifico group. The infarct volume and neurobehaviors were evaluated. Wholegene expression profiling was performed at different days after treatment (D1, D7, D14, D28) by RNA-seq. Differentially expressed genes (DEGs) were the processed for Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG). Some inflammation and immune related genes were screened and their expression was analyzed. Results: Compared to the Stroke plus Vehicle group and Bifico group, the infarct volume and neurological score were significantly reduced in the Pre-Bifico group. There were 2 DEGs at D1, 193 DEGs at D7, 70 DEGs at D28 between Stroke plus Pre-Bifico group and Stroke plus Vehicle group. For GO analysis, there were 139 significant terms at D7 and 195 at D28. For KEGG, there were 2 significant pathways at D7 and 9 at D28. Among 87 genes related to inflammation and immunity, 6 DEGs were identified. The expression of CCL9 was significantly elevated at most time points after stroke compared to the Stroke plus Vehicle group, while that of CCL6, CXCL10, CD48, CD72 and CLEC7A was highly expressed only in the recovery stage of stroke. Conclusion: Oral pre-treatment with Bifico for 28 days can reduce cerebral infarction and promote recovery of neurological function in stroke mice, which may be ascribed to the regulation of immunity and inflammation in the brain. [ABSTRACT FROM AUTHOR]

Cell transplantation therapy provides a regenerative strategy for neural repair. We tested the hypothesis that selective excitation of transplanted induced pluripotent stem cell-derived neural progenitor cells (iPS-NPCs) could recapitulate an activity-enriched microenvironment that confers regenerative benefits for the treatment of stroke. Mouse iPS-NPCs were transduced with a novel optochemogenetics fusion protein, luminopsin 3 (LM03), which consisted of a bioluminescent luciferase, Gaussia luciferase, and an opsin, Volvox Channelrhodopsin 1. These LM03-iPS-NPCs can be activated by either photostimulation using light or by the luciferase substrate coelenterazine (CTZ). In vitro stimulations of LM03-iPS-NPCs increased expression of synapsin-1, postsynaptic density 95, brain derived neurotrophic factor (BDNF), and stromal cell-derived factor 1 and promoted neurite outgrowth. After transplantation into the ischemic cortex of mice, LM03-iPS-NPCs differentiated into mature neurons. Synapse formation between implanted and host neurons was identified using immunogold electron microscopy and patch-clamp recordings. Stimulation of transplanted cells with daily intranasal administration of CTZ enhanced axonal myelination, synaptic transmission, improved thalamocortical connectivity, and functional recovery. Patch-clamp and multielectrode array recordings in brain slices showed that CTZ or light stimulation facilitated synaptic transmission and induced neuroplasticity mimicking the LTP of EPSPs. Stroke mice received the combined LM03-iPS-NPC/CTZ treatment, but not cell or CTZ alone, showed enhanced neural network connections in the peri-infarct region, promoted optimal functional recoveries after stroke in male and female, young and aged mice. Thus, excitation of transplanted cells via the noninvasive optochemogenetics treatment provides a novel integrative cell therapy with comprehensive regenerative benefits after stroke. [ABSTRACT FROM AUTHOR]

GluN3A or NR3A is a developmentally regulated N-methyl-D-aspartate receptor (NMDAR) subunit, showing a unique inhibitory role that decreases NMDAR current and the receptor-mediated Ca2+ influx. In the neonatal brain, GluN3A is shown to associate with synaptic maturation and spine formation and plays a neuroprotective role. Its functional role in the adult brain, however, is largely unknown. We tested the hypothesis that, disrespecting the relatively lower expression level of GluN3A in the adult brain, this inhibitory NMDAR subunit shows a protective action against ischemia-induced brain injury. In littermate wild-type (WT) and GluN3A knockout (KO) mice, focal cerebral ischemia was induced by permanent occlusion of right distal branches of the middle cerebral artery (MCA) plus 10-min ligation of both common carotid arteries (CCAs). Twenty-four hours after focal cerebral ischemia, the infarction volume assessed using 2,3,5-triphenyltetrazolium chloride (TTC) staining was significantly larger in GluN3A KO mice compared with WT mice. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining demonstrated enhanced cell death in GluN3A KO mice. Moreover, the deletion of GluN3A hindered sensorimotor functional recovery after stroke. It is suggested that, although the expression level is relatively lower in the adult brain, GluN3A is still a noteworthy regulator in ischemia-induced excitotoxicity and brain injury. [ABSTRACT FROM AUTHOR]

Background: Peripheral facial paralysis (PFP) is a common peripheral neural disease. Acupuncture treatment combined with PFP rehabilitation exercises is a routine method of PFP treatment. This article is to provide a new visual and objective evaluation method for exploring the mechanism and efficacy of acupuncture treatment on PFP, and develop an interactive augmented facial nerve function rehabilitation training system with multiple training models., Methods: This prospective and observational trial will recruit 200 eligible participants for the following study. In the trial, the laser speckle contrast analysis (LASCA) technology will be applied to monitor the microcirculation of facial blood flow during acupuncture, and real-time monitoring algorithms, data sampling, and digital imaging methods will be conducted by machine learning and image segmentation. Then, a database of patient facial expressions will be built, the correlation between surface blood flow perfusion volume and facial structure symmetry will be analyzed, combined with scale assessment and electrophysiological detection. In addition, we will also explore the objectivity and effectiveness of LASCA in the evaluation of facial paralysis (FP), and the changes in blood flow microcirculation before and after acupuncture treatment will be analyzed., Results: The standard image of the facial target area with facial nerve injury will be manually segmented by the convolutional neural network method. The blood flow images of the eyelid, cheek, and mandible of the patients' affected and healthy side will be compared and evaluated. Laser speckle blood flow symmetry Pr and its changes in FP condition evolution and prognosis outcome will be measured, and relevant characteristic signals values will be extracted. Finally, COX regression analysis method is conducted to establish a higher accuracy prediction model of FP with cross-validation based on laser speckle blood flow imaging technology., Conclusions: We use modern interdisciplinary high-tech technologies to explore the mechanism of acupuncture rehabilitation training in PFP. And we will provide evidence for the feasibility of using the LASCA technique as a typing diagnosis of FP in the acupuncture rehabilitation treatment of PFP., Registration Number: ChiCTR1800019463., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: Stem cell-based therapies are promising in regenerative medicine for protecting and repairing damaged brain tissues after injury or in the context of chronic diseases. Hypoxia can induce physiological and pathological responses. A hypoxic insult might act as a double-edged sword, it induces cell death and brain damage, but on the other hand, sublethal hypoxia can trigger an adaptation response called hypoxic preconditioning or hypoxic tolerance that is of immense importance for the survival of cells and tissues., Data Sources: This review was based on articles published in PubMed databases up to August 16, 2017, with the following keywords: "stem cells," "hypoxic preconditioning," "ischemic preconditioning," and "cell transplantation.", Study Selection: Original articles and critical reviews on the topics were selected., Results: Hypoxic preconditioning has been investigated as a primary endogenous protective mechanism and possible treatment against ischemic injuries. Many cellular and molecular mechanisms underlying the protective effects of hypoxic preconditioning have been identified., Conclusions: In cell transplantation therapy, hypoxic pretreatment of stem cells and neural progenitors markedly increases the survival and regenerative capabilities of these cells in the host environment, leading to enhanced therapeutic effects in various disease models. Regenerative treatments can mobilize endogenous stem cells for neurogenesis and angiogenesis in the adult brain. Furthermore, transplantation of stem cells/neural progenitors achieves therapeutic benefits via cell replacement and/or increased trophic support. Combinatorial approaches of cell-based therapy with additional strategies such as neuroprotective protocols, anti-inflammatory treatment, and rehabilitation therapy can significantly improve therapeutic benefits. In this review, we will discuss the recent progress regarding cell types and applications in regenerative medicine as well as future applications.

GluN3A or NR3A is a developmentally regulated N-methyl-d-aspartate receptor (NMDAR) subunit, showing a unique inhibitory role that decreases NMDAR current and the receptor-mediated Ca(2+) influx. In the neonatal brain, GluN3A is shown to associate with synaptic maturation and spine formation and plays a neuroprotective role. Its functional role in the adult brain, however, is largely unknown. We tested the hypothesis that, disrespecting the relatively lower expression level of GluN3A in the adult brain, this inhibitory NMDAR subunit shows a protective action against ischemia-induced brain injury. In littermate wild-type (WT) and GluN3A knockout (KO) mice, focal cerebral ischemia was induced by permanent occlusion of right distal branches of the middle cerebral artery (MCA) plus 10-min ligation of both common carotid arteries (CCAs). Twenty-four hours after focal cerebral ischemia, the infarction volume assessed using 2,3,5-triphenyltetrazolium chloride (TTC) staining was significantly larger in GluN3A KO mice compared with WT mice. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining demonstrated enhanced cell death in GluN3A KO mice. Moreover, the deletion of GluN3A hindered sensorimotor functional recovery after stroke. It is suggested that, although the expression level is relatively lower in the adult brain, GluN3A is still a noteworthy regulator in ischemia-induced excitotoxicity and brain injury.