Elevated microRNA-129-5p level ameliorates neuroinflammation and blood-spinal cord barrier damage after ischemia-reperfusion by inhibiting HMGB1 and the TLR3-cytokine pathway

摘要: Ischemia-reperfusion (IR) affects microRNA (miR) expression and causes substantial inflammation. Multiple roles of the tumor suppressor miR-129-5p in cerebral IR have recently been reported, but its functions spinal cord are unclear. Here, we investigated role after IR, particularly regulating high-mobility group box-1 (HMGB1) Toll-like receptor (TLR)-3 pathway. Ischemia was induced via 5-min occlusion aortic arch. The relationship between HMGB1 elucidated RT-PCR, western blotting, luciferase assays. cellular distribution determined double immunofluorescence. effect on HMGB1, TLR3, downstream cytokines evaluated using synthetic miRs, rHMGB1, TLR3 agonist Poly(I:C). Blood-spinal barrier (BSCB) permeability examined by measuring Evans blue (EB) dye extravasation water content. temporal profiles assay results indicated that targeted HMGB1. Compared with Sham group, had higher immunoreactivity, which primarily distributed neurons microglia. Intrathecal injection mimic significantly decreased interleukin (IL)-1β necrosis factor (TNF)-α levels double-labeled cell count 48 h post-surgery, whereas rHMGB1 Poly(I:C) reversed these effects. Injection preserved motor function prevented BSCB leakage based increased Basso Mouse Scale scores EB content, aggravated injuries. Increasing protect against ameliorating inflammation-induced neuronal BCSB damage inhibiting TLR3-associated cytokines.