Journal
JOURNAL OF NEUROINFLAMMATION
Volume 14, Issue -, Pages -Publisher
BIOMED CENTRAL LTD
DOI: 10.1186/s12974-017-0977-4
Keywords
Blood-spinal cord barrier; High-mobility group box-1; Ischemia-reperfusion injury; MicroRNAs; Toll-like receptor 3
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Funding
- National Natural Science Foundation of China [81601053, 81401000]
- Scientific Research Project of Liaoning Province Department of Education [LK201636]
- Science and Technology Program of Liaoning [2012408002]
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Background: 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 in the spinal cord are unclear. Here, we investigated the role of miR-129-5p after spinal cord IR, particularly in regulating high-mobility group box-1 (HMGB1) and the Toll-like receptor (TLR)-3 pathway. Methods: Ischemia was induced via 5-min occlusion of the aortic arch. The relationship between miR-129-5p and HMGB1 was elucidated via RT-PCR, western blotting, and luciferase assays. The cellular distribution of HMGB1 was determined via double immunofluorescence. The effect of miR-129-5p on the expression of HMGB1, TLR3, and downstream cytokines was evaluated using synthetic miRs, rHMGB1, and the TLR3 agonist Poly(I:C). Blood-spinal cord barrier (BSCB) permeability was examined by measuring Evans blue (EB) dye extravasation and the water content. Results: The temporal miR-129-5p and HMGB1 expression profiles and luciferase assay results indicated that miR-129-5p targeted HMGB1. Compared with the Sham group, the IR group had higher HMGB1 immunoreactivity, which was primarily distributed in neurons and microglia. Intrathecal injection of the miR-129-5p mimic significantly decreased the HMGB1, TLR3, interleukin (IL)-1 beta and tumor necrosis factor (TNF)-alpha levels and the double-labeled cell count 48 h post-surgery, whereas rHMGB1 and Poly(I: C) reversed these effects. Injection of miR-129-5p mimic preserved motor function and prevented BSCB leakage based on increased Basso Mouse Scale scores and decreased EB extravasation and water content, whereas injection rHMGB1 and Poly(I: C) aggravated these injuries. Conclusions: Increasing miR-129-5p levels protect against IR by ameliorating inflammation-induced neuronal and BCSB damage by inhibiting HMGB1 and TLR3-associated cytokines.
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