Neuroprotective Effects of Simvastatin and Cilostazol in L-Methionine-Induced Vascular Dementia in Rats

Abstract

Vascular dementia (VaD) is a degenerative cerebrovascular disorder that leads to progressive decline in cognitive abilities and memory. Several reports demonstrated that oxidative stress and endothelial dysfunction are principal pathogenic factors in VaD. The present study was constructed to determine the possible neuroprotective effects of simvastatin in comparison with cilostazol in VaD induced by L-methionine in rats. Male Wistar rats were divided into four groups. Group I (control group), group II received L-methionine (1.7 g/kg, p.o.) for 32 days. The remaining two groups received simvastatin (50 mg/kg, p.o.) and cilostazol (100 mg/kg, p.o.), respectively, for 32 days after induction of VaD by L-methionine. Subsequently, rats were tested for cognitive performance using Morris water maze test then sacrificed for biochemical and histopathological assays. L-methionine induced VaD reflected by alterations in rats' behavior as well as the estimated neurotransmitters, acetylcholinesterase activity as well as increased brain oxidative stress and inflammation parallel to histopathological changes in brain tissue. Treatment of rats with simvastatin ameliorated L-methionine-induced behavioral, neurochemical, and histological changes in a manner comparable to cilostazol. Simvastatin may be regarded as a potential therapeutic strategy for the treatment of VaD. To the best of our knowledge, this is the first study to reveal the neuroprotective effects of simvastatin or cilostazol in L-methionine-induced VaD. Graphical Abstract ᅟ.

Keywords: Acetylcholinesterase; Cilostazol; L-methionine; Oxidative stress; Simvastatin; Vascular dementia.