miR-26a Improves Microglial Activation and Neuronal Apoptosis in a Rat Model of Cerebral Infarction by Regulating the TREM1-TLR4/MyD88/NF-κB Axis.

Abstract

Emerging studies have indicated that abnormally expressed microRNAs (miRNAs) are related to the pathogenesis of cerebral ischemia. Nevertheless, the function of miR-26a in neuronal damage and microglial activation during cerebral infarction remains elusive. It was revealed that miR-26a was downregulated in oxygen-glucose deprivation (OGD)-treated microglia and neurons. Overexpressing miR-26a reduced the inflammatory reaction in BV2 cells and decreased neuronal apoptosis following OGD stimulation. miR-26a upregulation inactivated the TLR4/MyD88/NF-κB pathway and inhibited TREM1 expression. Repressing NF-κB phosphorylation inhibited the miR-26a level. As supported by the dual-luciferase reporter assay, TREM1 was directly targeted by miR-26a. Furthermore, a rat model of middle cerebral artery occlusion (MCAO) was built. We discovered that miR-26a improved cognitive, learning, and motor functions and reduced cerebral edema in MCAO rats. Mechanistically, upregulating miR-26a reduced inflammation and neuronal apoptosis by mitigating the TREM1-TLR4/MyD88/NF-κB pathway in the MCAO rat model. Collectively, this study verified that the miR-26a-TREM1-TLR4/MyD88/NF-κB axis contributes to modulating OGD-mediated microglial activation and neuronal injury.