miR-92a Agomir protects against ischemic stroke by suppressing oxidative stress, inflammation, excitotoxicity, and p53-mediated apoptosis.

Abstract

Various microRNAs (miRs) have long served as therapeutic targets for ischemic stroke, so we aimed to assess whether miR-92a-3p protects against cerebral ischemia and identify downstream targets in an animal model. For this purpose, rats were randomly divided into sham, middle cerebral artery occlusion (MCAO), miR-92a Agomir+MCAO, and miR-92a Antagomir+MCAO groups. Twenty-four hours before MCAO surgery, rno-miR-92a-3p Agomir or Antagomir (100µM) were injected into the right striatum of rats. Neurological deficit, infarction, blood-brain barrier (BBB), cerebral edema, oxidative stress and inflammation-related factors mRNA expression (GCH1, GRIN1, NOS1, and NOX1), and the activities of antioxidant enzymes (SOD and CAT), and GSSG in the piriform cortex-amygdala, striatum, and cortex areas were evaluated. Immunohistochemistry was used to count positive cells of TNF-α and p53, and H&E staining served to examine histological alterations. Significant reductions in neurological deficit, infarction volume, edema, and BBB permeability were observed in the miR-92a Agomir+MCAO group compared to the MCAO group. miR-92a Agomir significantly down-regulated the expression of GCH1, GRIN1, NOS1, NOX1, TNF-α, and p53. The activities of antioxidant enzymes were elevated following administration of miR-92a Agomir. Moreover, miR-92a Agomir could attenuate the GSSG levels. While the preconditioning paradigm limits direct clinical translation, these mechanistic insights provide a compelling rationale for evaluating delayed administration strategies in future translational studies.