miRNA-105 Attenuates Hypoxic-Ischemic Brain Damage in Neonatal Rats by Inhibiting Apoptosis and Necroptosis

Abstract

Apoptosis and necroptosis contribute significantly to cell death in hypoxic-ischemic encephalopathy (HIE). While microRNA-105 (miR-105) is known to suppress both apoptosis and necroptosis in cardiac ischemia, its role in HIE remains unclear. This study investigated the effects of miR-105 on apoptosis and necroptosis in a neonatal rat model of HIE. MiR-105 agomir was administered intracerebroventricularly 6 h post-hypoxic-ischemia (HI). The characteristic apoptosis-related proteins (BNIP3, cleaved caspase 3), necroptosis mediators (RIP3, p-RIP3, p-RIP1, p-MLKL), cerebral infarction, and neurological deficits were analyzed. Results showed miR-105 was significantly downregulated in cerebral cortex from 6 to 48 h post-HI, concurrent with increased BNIP3 and RIP3 expression, and elevated apoptosis and necroptosis, at both 24 and 48 h. MiR-105 agomir treatment suppressed BNIP3 and RIP3 expression, reduced apoptosis and necroptosis, attenuated infarct volume, lowered neurological severity score, and improved spatial learning and memory abilities. In conclusion, miR-105 alleviates HI brain injury in neonatal rats by simultaneously inhibiting apoptosis and necroptosis, highlighting its potential as therapeutic agent for HIE.

Keywords: Apoptosis; Hypoxic-ischemic; MiRNA; Necroptosis.