Simvastatin Alleviates Vascular Cognitive Impairment Caused by Lacunar Cerebral Infarction Through Protein Kinase B/Nuclear Factor Erythroid 2–Related Factor 2 (AKT/Nrf2) Signaling Pathway

Abstract

Lacunar cerebral infarction (LACI) is one of the main causes of vascular cognitive impairment (VCI). Herein, this study explored the potential effect of Simvastatin (Sim) on VCI secondary to LACI and Akt/Nrf2 signaling transduction and apoptosis. We established a rat model of VCI and the animals were administered with Sim (40 mg/kg and 80 mg/kg) every day for 28 days. After that, the cognition and memory abilities of rats were assessed together with analysis of morphological changes of hippocampal neurons by immunohistochemistry staining and level of anti-apoptotic related proteins and Akt and Nrf2 signaling proteins by western blot. Compared with normal saline (control group), Sim administration significantly improved the capacity spatial learning and relieved the memory impairment with an improvement in morphological defects. Importantly, Sim treatment restored the p-Akt, t-Nrf2, n-Nrf2 and HO-1 expression along with up-regulation of Bcl-2 and down-regulation of Bax. In conclusion, Sim improves cognitive and morphological disorders induced by LACI possibly through regulating Akt/Nrf2 signaling pathway. These evidence might promote the development of Sim-based treatment for VCI and LACI.