miR-92a Agomir protects against ischemic stroke by suppressing oxidative stress, inflammation, excitotoxicity, and p53-mediated apoptosis.
TL;DR
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, providing a compelling rationale for evaluating delayed administration strategies in future translational studies.
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.