Neuroprotective Effects of Nicorandil in Chronic Cerebral Hypoperfusion-Induced Vascular Dementia

Abstract

Ischemia-induced chronic cerebral hypoperfusion (CCH) is associated with reduced cerebral blood flow and vascular dementia (VaD). Brain mitochondrial potassium (adenosine triphosphate-sensitive potassium [KATP]) channels have a beneficial role in various brain conditions. The utility of KATP channels in CCH-induced VaD is still unknown. The aim of this study is to investigate the role of nicorandil, a selective KATP channel opener, in CCH-induced VaD. The method of 2-vessel occlusion (2VO) was used to induce CCH in mice. Cognitive impairment was assessed using Morris water maze. Serum nitrosative stress (nitrite/nitrate), brain cholinergic dysfunction (acetylcholinesterase [AChE] activity), brain oxidative stress (thiobarbituric acid reactive substances, glutathione [GSH], catalase [CAT], and superoxide dismutase [SOD]), inflammation (myeloperoxidase [MPO]), and infarct size (2,3,5-triphenyltetrazolium chloride staining) were assessed. 2-vessels-occluded animals have shown significant cognitive impairment, serum nitrosative stress (reduced nitrite/nitrate), cholinergic dysfunction (increased brain AChE activity), and increased brain oxidative stress (reduction in GSH content and SOD and CAT activities with a significant increase in lipid peroxidation), along with a significant increase in MPO activity and infarct size. However, nicorandil treatment has significantly attenuated various CCH-induced behavioral and biochemical impairments. It may be said that 2VO provoked CCH leading to VaD, which was attenuated by the treatment of nicorandil. So, modulation of KATP channels may provide benefits in CCH-induced VaD.