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Neuroprotective Effects of Nicorandil in Chronic Cerebral Hypoperfusion-Induced Vascular Dementia
Surbhi Gupta1, Prabhat Singh1, Bhupesh Sharma1
1Department of Pharmacology, School of Pharmacy, BIT, Meerut, India; Department of Pharmacology, Amity Institute of Pharmacy, Amity University, Noida, India.
Insights
Nicorandil, a KATP channel opener, improved cognitive function and reduced oxidative stress in mice with chronic cerebral hypoperfusion (CCH)-induced vascular dementia (VaD). This suggests KATP channel modulation may treat VaD.
Area of Science:
- Neuroscience
- Pharmacology
- Vascular Biology
Background:
- Chronic cerebral hypoperfusion (CCH) reduces blood flow, leading to vascular dementia (VaD).
- Brain mitochondrial potassium (adenosine triphosphate-sensitive potassium [KATP]) channels are implicated in neurological conditions.
- The role of KATP channels in CCH-induced VaD remains unclear.
Purpose of the Study:
- To investigate the therapeutic potential of nicorandil, a selective KATP channel opener, in a mouse model of CCH-induced VaD.
Main Methods:
- Chronic cerebral hypoperfusion (CCH) was induced in mice using 2-vessel occlusion (2VO).
- Cognitive function was evaluated using the Morris water maze.
- Biochemical markers of nitrosative stress, cholinergic dysfunction, oxidative stress, inflammation, and infarct size were assessed.
Main Results:
- 2VO induced significant cognitive impairment, nitrosative stress, cholinergic dysfunction, oxidative stress, inflammation, and increased infarct size.
- Nicorandil treatment markedly attenuated these behavioral and biochemical deficits caused by CCH.
Conclusions:
- 2VO-induced CCH leads to vascular dementia (VaD) in mice.
- Nicorandil treatment effectively mitigated the adverse effects of CCH-induced VaD.
- Modulating KATP channels represents a potential therapeutic strategy for CCH-induced VaD.
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 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.
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 KATP channels may provide benefits in CCH-induced VaD.
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