High-Frequency Repetitive Transcranial Magnetic Stimulation (rTMS) Protects Against Ischemic Stroke by Inhibiting M1 Microglia Polarization through Let-7b-5p/HMGA2/NF-κB Signaling Pathway

ABSTRACT: Modulating M1/M2 polarization is a potential therapy for treating ischemic stroke. Repetitive transcranial magnetic stimulation (rTMS) held the capacity to regulate astrocytic polarization, but little is known about rTMS effects on microglia. Therefore, the present study aimed to investigate whether and how rTMS influence microglia polarization in ischemic stroke models. The 10-Hz rTMS was applied to transient middle cerebral artery occlusion (MCAO) rats and oxygen and glucose deprivation/ reoxygenation injured BV2 cells. Western blot, immunofluorescence and ELISA were used to detect M1/M2 markers. High-throughput sequencing, RT-PCR and FISH staining were adopted to test microRNA changes. The 10-Hz rTMS inhibited ischemia/reperfusion induced M1 microglia and significantly increased let-7b-5p. HMGA2 was proved to be the target protein of let-7b-5p and its downstream NF-κB signaling pathway were inhibited by rTMS. Microglia culture medium (MCM) collected from rTMS treated microglia had low TNF-α but high IL-10 concentration, leading to reduced neural death, minor ischemic volumes and improved functional recovery of MCAO animals. However, knockdown of let-7b-5p by antagomir reversed rTMS effects on microglia. In conclusion, high-frequency rTMS could improve functional recovery through inhibiting M1 microglia polarization via regulating let-7b-5p/HMGA2/NF-κB signaling pathway in cerebral ischemic stroke models.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE192910 | GEO | 2022/08/10

REPOSITORIES: GEO