Simvastatin mitigates vascular cognitive impairment in rat’s hippocampus in lacunar cerebral infarction

Abstract

Simvastatin is used to treat Alzheimer’s disease with impaired cognitive function through blocking of PI3K/Akt signaling to inhibit survival of new neurons and growth of neurons. This study investigated the potential of simvastatin on vascular cognitive impairment (VCI) caused by lacunar cerebral infarction (LCI) in the hippocampus of rats. After establishment of LCI models, rats were administered with NaOH solution (model group), simvastatin (simvastatin group), and PI3K/Akt pathway inhibitor (inhibitor group), respectively, and 10 healthy rats served as control group. Upon treatment, Y-maze and Morris water maze detected spatial cognition ability of rats; while cleaved caspase-3 staining was used to assess apoptosis in the hippocampus. Western blot analysis detected Akt and ERK1/2 phosphorylation levels and enzyme-linked immuno sorbent assay (ELISA) determined the content of brain-derived neurotrophic factor (BDNF). The Y maze Morris water maze confirmed impairment of long-term memory abilities in the LCI rats from the model group. Treatment with simvastatin significantly improved correct rate of arm alternates in rats and shorted the stage latency in the hidden platform experiment. The number of apoptotic cells increased in the hippocampal DG sub-granular area of rats with LCI, and BDNF level was significantly reduced. Administration of simvastatin suppressed cell apoptosis and increased BDNF level when improving phosphorylation level of Akt and ERK1/2 as well. Cerebral ischemia following LCI affects short and long-term memory, which leads to VCI. Simvastatin increases Akt and ERK1 in PI3K/Akt pathway, and hence up-regulates hippocampal BDNF levels, which promotes the regeneration of rat hippocampal nerve cells to relieve VCI.