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Effects of Exosomes on Neurological Function Recovery for Ischemic Stroke in Pre-clinical Studies: A Meta-analysis.

ABSTRACT: Background: Exosomes, especially stem cell-derived exosomes, have been widely studied in pre-clinical research of ischemic stroke. However, their pooled effects remain inconclusive. Methods: Relevant literature concerning the effects of exosomes on neurological performance in a rodent model of ischemic stroke was identified via searching electronic databases, including PubMed, Embase, and Web of Science. The primary outcomes included neurological function scores (NFS) and infarct volume (IV), and the secondary outcomes were several pro-inflammatory factors and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling-positive cells. Subgroup analyses regarding several factors potentially influencing the effects of exosomes on NFS and IV were also conducted. Results: We identified 21 experiments from 18 studies in the meta-analysis. Pooled analyses showed the positive and significant effects of exosomes on NFS (standardized mean difference -2.79; 95% confidence interval -3.81 to -1.76) and IV (standardized mean difference -3.16; 95% confidence interval -4.18 to -2.15). Our data revealed that the effects of exosomes on neurological outcomes in rodent stroke models might be related to routes of administration and exosomes sources. In addition, there was significant attenuation in pro-inflammatory factors, including interleukin-6, tumor necrosis factor-? and interleukin-1?, and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling-positive cells when undergoing exosomes treatment. Conclusion: Cell-derived exosomes treatment demonstrated statistically significant improvements in structural and neurological function recovery in animal models of ischemic stroke. Our results also provide relatively robust evidence supporting cell-derived exosomes as a promising therapy to promote neurological recovery in stroke individuals.

SUBMITTER: Huang M

PROVIDER: S-EPMC7726242 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Effects of Exosomes on Neurological Function Recovery for Ischemic Stroke in Pre-clinical Studies: A Meta-analysis.

Huang Mudan M Hong Zhongqiu Z Xiao Chongjun C Li Lili L Chen Lilin L Cheng Shimei S Lei Tingting T Zheng Haiqing H

Frontiers in cellular neuroscience 20201126

<b>Background:</b> Exosomes, especially stem cell-derived exosomes, have been widely studied in pre-clinical research of ischemic stroke. However, their pooled effects remain inconclusive. <b>Methods:</b> Relevant literature concerning the effects of exosomes on neurological performance in a rodent model of ischemic stroke was identified via searching electronic databases, including PubMed, Embase, and Web of Science. The primary outcomes included neurological function scores (NFS) and infarct v ...[more]

PMID: 33324166

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Project description:ObjectiveIschemic stroke (IS) is a common disease that causes severe and long-term neurological disability in people worldwide. Although rehabilitation is indispensable to promote neurological recovery in ischemic stroke, it is limited to providing a timely and efficient reference for developing and adjusting treatment strategies because neurological assessment after stroke treatment is mostly performed using scales and imaging. Therefore, there is an urgent need to find biomarkers that can help us evaluate and optimize the treatment plan.MethodsWe used data-independent acquisition (DIA) technology to screen differentially expressed proteins (DEPs) before and after ischemic stroke rehabilitation treatment, and then performed Gene Ontology (GO) and pathway enrichment analysis of DEPs using bioinformatics tools such as KEGG pathway and Reactome. In addition, the protein-protein interaction (PPI) network and modularity analysis of DEPs were integrated to identify the hub proteins (genes) and hub signaling pathways for neurological recovery in ischemic stroke. PRM-targeted proteomics was also used to validate some of the screened proteins of interest.ResultsAnalyzing the serum protein expression profiles before and after rehabilitation, we identified 22 DEPs that were upregulated and downregulated each. Through GO and pathway enrichment analysis and subsequent PPI network analysis constructed using STRING data and subsequent Cytoscape MCODE analysis, we identified that complement-related pathways, lipoprotein-related functions and effects, thrombosis and hemostasis, coronavirus disease (COVID-19), and inflammatory and immune pathways are the major pathways involved in the improvement of neurological function after stroke rehabilitation.ConclusionComplement-related pathways, lipoprotein-related functions and effects, thrombosis and hemostasis, coronavirus disease (COVID-19), and inflammation and immunity pathways are not only key pathways in the pathogenesis of ischemic stroke but also the main pathways of action of rehabilitation therapy. In addition, IGHA1, LRG1, IGHV3-64D, and CP are upregulated in patients with ischemic stroke and downregulated after rehabilitation, which may be used as biomarkers to monitor neurological impairment and recovery after stroke.

Dataset Information

Effects of Exosomes on Neurological Function Recovery for Ischemic Stroke in Pre-clinical Studies: A Meta-analysis.

Publications

Effects of Exosomes on Neurological Function Recovery for Ischemic Stroke in Pre-clinical Studies: A Meta-analysis.

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