Traumatic brain injury (TBI) is an urgent global health issue. Neuroinflammation, due partially to microglia, can worsen or even cause neuropsychiatric disorders after a TBI. An increasing number of studies have found that adipose-derived stem cell (ADSC) derived exosomes can alleviate many diseases by delivering non-coding RNAs including circRNA and miRNAs, but the mechanism of action remains unclear.
In the present investigation, we produced a TBI mouse model and isolated exosomes from their ADSCs before and after an hypoxic pretreatment. We then used next generation sequencing (NGS) to identify differentially expressed circRNAs and luciferase report assays to determine the relationship between the different noncoding RNAs (miRNA, circRNA and mRNA).
The results show that we successfully isolated ADSCs which possessed a multidirectional differentiation potential. We then isolated exosomes from untreated ADSCs (Exos) and from hypoxia pretreated ADSCs (HExos). The HExos significantly decreased hippocampal nerve injury after TBI by decreasing M1 microglia mediated inflammatory cytokine expression and caused recovery of cognitive function. NGS data revealed that abnormal circ-Scmh1 expression plays a role in HExo mediated brain tissue preservation after TBI. Furthermore, luciferase report analysis found that miR-154-5p and STAT6 were the targets for circ-Scmh1. Interestingly, miR-154-5p overexpression or STAT6 inhibition reversed the circ-Scmh1 induced M2 microglial polarization. Overexpression of circ-Scmh1 increased the therapeutic effect of Exo on hippocampal nerve injury after TBI by promotion of M2 microglial polarization and decreased inflammatory induced hippocampal nerve injury.
Taken together, we found that exosomes from ADSCs ameliorate nerve damage in the hippocampus post TBI through the delivery of circ-Scmh1 and the promotion of microglial M2 polarization.
Copyright © 2023. Published by Elsevier Ltd.
