MicroRNA-132 Alleviates Ischemia-Reperfusion-Induced Neuronal Apoptosis by Targeting Mecp2 in Stroke Models.

Cerebral ischemia-reperfusion injury (CI/RI) remains a significant challenge in ischemic stroke treatment, often leading to exacerbated neuronal apoptosis and poor neurological recovery despite successful recanalization. MicroRNAs (miRNAs) are known to influence neurodegeneration and repair through post-transcriptional modulation of apoptosis-related genes. In this study, we investigated the neuroprotective role of miR-132 and its interaction with the epigenetic regulator Mecp2 under CI/RI conditions. Utilizing a rat MCAO model and SH-SY5Y neuronal cells exposed to OGD/R, we found that miR-132 levels were significantly decreased while Mecp2 expression was elevated following ischemic injury. Functional assays revealed that overexpression of miR-132 restored neuronal viability, increased anti-apoptotic Bcl-2, and reduced pro-apoptotic Bax expression. In contrast, inhibition of miR-132 exacerbated apoptosis. Bioinformatic analysis and dual-luciferase reporter assays confirmed that miR-132 directly targets the 3′UTR of Mecp2. Importantly, Mecp2 overexpression abolished the protective effects of miR-132, indicating that this axis is essential for apoptosis modulation. These findings establish the miR-132/Mecp2 axis as a key determinant of neuronal fate in CI/RI and identify it as a promising target for neuroprotective therapies. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12640-026-00796-0.