Neuroprotective Effects of Nicorandil in Chronic Cerebral Hypoperfusion-Induced Vascular Dementia.
BACKGROUND
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 KATPchannels in CCH-induced VaD is still unknown. The aim of this study is to investigate the role of nicorandil, a selective KATPchannel opener, in CCH-induced VaD.


METHODS
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.


RESULTS
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.


CONCLUSIONS
It may be said that 2VO provoked CCH leading to VaD, which was attenuated by the treatment of nicorandil. So, modulation of KATPchannels may provide benefits in CCH-induced VaD.
Department of Pharmacology, School of Pharmacy, BIT, Meerut, India; Department of Pharmacology, Amity Institute of Pharmacy, Amity University, Noida, India.
Surbhi
S
Gupta
Department of Pharmacology, School of Pharmacy, BIT, Meerut, India; Department of Pharmacology, Amity Institute of Pharmacy, Amity University, Noida, India.
Prabhat
P
Singh
Department of Pharmacology, School of Pharmacy, BIT, Meerut, India; Department of Pharmacology, Amity Institute of Pharmacy, Amity University, Noida, India. Electronic address: drbhupeshresearch@gmail.com.
Bhupesh
B
Sharma
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology; D002374:Catalase / Q000378:metabolism; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D003071:Cognition / Q000187:drug effects; D015140:Dementia, Vascular / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control* / Q000523:psychology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D058851:GPI-Linked Proteins / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D054086:KATP Channels / Q000819:agonists / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D018696:Neuroprotective Agents / Q000494:pharmacology*; D020108:Nicorandil / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D013997:Time Factors
D058851:GPI-Linked Proteins; D018836:Inflammation Mediators; D054086:KATP Channels; D018696:Neuroprotective Agents; D017392:Thiobarbituric Acid Reactive Substances; D020108:Nicorandil; D002374:Catalase; D009195:Peroxidase; D013482:Superoxide Dismutase; D000110:Acetylcholinesterase; C548245:Ache protein, mouse; D005978:Glutathione
2,3,5-Triphenylterazolium chloride staining; 2-vessel occlusion; acetylcholinesterase; nicorandil; oxidative stress