miR-766-3p regulates neurological deficits and inflammation after cerebral hemorrhage by targeting bradykinin receptor B2.

Abstract

OBJECTIVE: This study aims to clarify the protective effect of miR-766-3p on brain injury caused by intracerebral hemorrhage (ICH), and to reveal the mechanisms by which it regulates neural function, neuroinflammation, and brain edema. METHODS: An ICH rat model was constructed and PC12 cells were treated with hemin to simulate neuronal injury. Quantitative reverse transcription PCR was used to detect the expression of miR-766-3p and inflammatory factors. Cell counting kit-8 and flow cytometry were used to assess cell viability and apoptosis. Brain edema was evaluated by the dry-wet method. Neurological function was assessed through the Garcia score, forelimb placement test, and corner turn test. The dual-luciferase reporter assay and RNA immunoprecipitation were employed to validate the targeting relationship between miR-766-3p and bradykinin receptor B2 (BDKRB2). RESULTS: The expression of miR-766-3p was significantly downregulated in the brain tissue surrounding the hematoma and PC12 cells. Overexpression of miR-766-3p increased the survival rate of neuronal cells, inhibited apoptosis, and reduced the release of inflammatory factors. In vivo experiments demonstrated that this intervention measure improved neurological function scores and placement rate of the forelimbs while alleviating turning disorders, brain edema, and neuroinflammation. miR-766-3p directly targets BDKRB2 and inhibits its expression. Overexpression of BDKRB2 completely reversed the neuroprotective effects of miR-766-3p. CONCLUSION: miR-766-3p alleviates neuroinflammation, cerebral edema, and neuronal damage caused by ICH by targeting and inhibiting BDKRB2.