Pharmacological modulation of I₁-imidazoline and 伪₂-adrenoceptors in sub acute brain ischemia induced vascular dementia

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• 作者：Surbhi Gupta ; Bhupesh Sharma
• 关键词：2VO ; bilateral common carotid arteries ligation or two vessel occlusion ; AChE ; acetylcholinesterase ; AD ; Alzheimer's disease ; CAT ; catalase ; CCH ; chronic cerebral hypo perfusion ; CMC ; carboxy-methylcellulose ; CPCSEA ; Committee for the Purpose of Control and Supervision of Experiments on Animals ; DTNB ; 5 ; 5'-dithiobis (2-nitrobenzoic acid) ; ELT ; Eescape latency time ; GSH ; glutathione ; IAEC ; Institutional animal ethics committees ; MDA ; malondialdehyde ; MWM ; Morris water maze ; NBT ; nitrobluetetrazo
• 刊名：European Journal of Pharmacology
• 出版年：15 January, 2014
• 年：2014
• 卷：723
• 期：Complete
• 页码：80-90
• 全文大小：1602 K

文摘

Sub-acute brain ischemia is a risk factor for the development of vascular dementia (VaD). Sub-acute brain ischemia induced VaD, participates in a negative role in impaired cognition. Imidazoline receptors are widely expressed in the central nervous system. But the role of I₁-imidazoline and 伪₂-adrenoceptors in VaD are still unknown. The present study has been designed to investigate the role of selective I₁-imidazoline receptor modulator; moxonidine as well as 伪₂-adrenoceptor modulator; clonidine in sub-acute brain ischemia induced VaD in mice (n=8). Permanent bilateral common carotid arteries ligation (2VO) technique was used to induce sub-acute brain ischemia in mice. Assessment of spatial learning and memory was done by using Morris water maze. Brain damage was assessed as percent infarct, using TTC staining of brain coronal sections. Oxidative stress was assessed by estimating brain malondialdehyde (MDA), catalase (CAT), glutathione (GSH) and superoxide dismutase (SOD). Cholinergic status was assessed by brain acetylcholinesterase (AChE) activity. 2VO animals have shown significant reduction in learning and memory as well as brain CAT, GSH and SOD, with significant increase in brain infarct size, MDA and AChE activity. Whereas, administration of moxonidine and clonidine significantly attenuated 2VO induced learning and memory deficits, brain damage, brain oxidative stress and higher AChE activity. It may be concluded that 2VO induced sub-acute brain ischemia has elicited dementia, which was attenuated by moxonidine and clonidine. Thus, modulators of I₁-imidazoline receptors may be explored further for their benefits in sub-acute brain ischemia induced vascular dementia.