MiR-140-5p Attenuates Neuroinflammation and Brain Injury in Rats Following Intracerebral Hemorrhage by Targeting TLR4.

Abstract

The Toll-like receptor 4 (TLR4)-mediated neuroinflammation plays a key role in inducing secondary brain injury after intracerebral hemorrhage (ICH). However, how TLR4 is regulated during this pathological process is not well understood. In the present study, by taking advantage of a rat ICH model, we show that miR-140-5p is reversely correlated with TLR4 expression in the peri-hematomal striatum following ICH. In vitro, miR-140-5p directly targets TLR4 and suppresses its expression in a rat neuronal PC12 cell line. Moreover, an intracerebral ventricular injection of miR-140-5p mimics improves neurological function and reduces apoptotic cell death and limits the production of inflammatory cytokines following ICH, indicating that miR-140-5p attenuates brain injury and neuroinflammation in vivo. Furthermore, miR-140-5p suppresses TLR4 expression and inhibits the downstream MyD88/TRIF inflammatory pathway and NF-κB activity following ICH, suggesting that the inhibition of TLR4-mediated neuroinflammation at least in part accounts for the neuroprotective role of miR-140-5 against ICH-induced brain injury in rats. Collectively, these results identify miR-140-5 as a negative regulator of TLR4 and downstream inflammatory pathway following ICH, implicating that miR-140-5 might represent as a potential therapeutic target for alleviating ICH-induced brain injury.