MicroRNA-132 attenuates neurobehavioral and neuropathological changes associated with intracerebral hemorrhage in mice

- MiR-132 alleviated inflammatory reactions after ICH.
- MiR-132 attenuated cell death after ICH.
- MiR-132 potentiates the cholinergic anti-inflammatory pathway by targeting AChE.

Recent studies suggest that microRNA-132 (miR-132) potentiates the cholinergic blockade of inflammatory reactions by targeting acetylcholinesterase (AChE) and affords robust protection against ischemia-induced neuronal death. However, the role of miR-132 in intracerebral hemorrhage (ICH) remains unexplored. This study aimed to determine whether miR-132 participates in the process and launches an anti-inflammatory response in a mouse model of ICH. To establish a relationship between miR-132 and ICH-induced neuronal inflammation and death, we used unilateral stereotaxic injections to deliver lentiviruses encoding miR-132, anti-miR-132 or an empty lentiviral vector directly into the right caudate nuclei of 192 living male C57BL/6 mice. Fourteen days later, ICH was induced by injection of autologous blood into these three groups. Neurodeficits, brain edema, blood-brain barrier (BBB) integrity, inflammatory reactions, together with cell death were assessed after ICH. Compared with the control group, the mice overexpressing miR-132 in the brain responded with attenuated neurological deficits and brain edema. The counts of activated microglia and the expression of proinflammatory cytokines were also decreased in these mice. Additionally, BBB integrity improved, and the extent of neuronal death decreased in ICH mice injected with lentivirus encoding miR-132. On the contrary, a decrease of miR-132 expression aggravated the severity of inflammation and increased cell apoptosis. Overall, these findings support a protective role of miR-132 in a mouse model of ICH, providing new opportunities for therapeutic intervention.