Nimodipine ameliorates cognitive dysfunction and neurological injury after subarachnoid hemorrhage in rats by upregulating microRNA-31-5p targeting hypoxia-inducible factor 1 subunit alpha inhibitor.

Abstract

Subarachnoid hemorrhage (SAH) is a hemorrhagic stroke with high short-term mortality that can lead to cognitive and neurological impairment. Accurate and appropriate treatment strategies are urgently needed. Nimodipine (NDP) can not only improve blood circulation in SAH patients but also repair ischemic neuronal damage. microRNAs (miRNAs) are abundantly expressed in the brain and are involved in brain injury. Therefore, this study investigated the possible regulatory mechanisms of nimodipine on miRNAs in the process of cognitive dysfunction and neurological injury after SAH. The SAH rat model was established, miR-31-5p and hypoxia-inducible factor 1 subunit alpha inhibitor (HIF1AN) expressions were detected 48 h after modeling, and neurobehavioral function, neuronal apoptosis, activation of microglia, and inflammation were evaluated. Finally, the targeting relationship between miR-31-5p and HIF1AN was verified. The study findings explained that NDP treatment could effectively improve cognitive dysfunction, brain injury, neuronal injury, and neuroinflammation in SAH rats. SAH rats expressed down-regulated miR-31-5p and up-regulated HIF1AN. Overexpressing miR-31-5p or knocking down HIF1AN ameliorated cognitive dysfunction and brain damage in SHA rats. Mechanistically, nimodipine can promote miR-31-5p expression, and HIF1AN took part in the development of SAH as a downstream target gene of miR-31-5p. In conclusion, NDP ameliorates cognitive dysfunction and neurological damage in SHA rats by miR-31-5p/HIF1AN axis.