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Abstract

Objectives: Chronic cerebral hypoperfusion (CCH) is a general pathophysiological condition occurring in vascular dementia (VaD) associated with negative impact on cognitive functions. Cysteinyl leukotriene-1 receptors (CysLT1R) are extensively present in the central nervous system, where they participate in regulation of cognition, motivation, inflammation and neurodegeneration. The purpose of this study is to examine the role of montelukast; a specific CysLT1 antagonist in CCH induced VaD in mice. Methods: Two vessel occlusion (2VO) or permanent ligation of bilateral common carotid arteries technique was used to induce CCH in mice. Animals were assessed for learning and memory (Morris water maze), cholinergic function (increased acetylcholinesterase activity), brain inflammation, brain oxidative stress (brain superoxide dismutase, glutathione, catalase and thiobarbituric acid reactive substance level) and brain damage (brain infarct size using 2, 3, 5-triphenylterazolium chloride staining). Results: Animals with bilateral carotid arteries occlusion have revealed impaired learning and memory, cholinergic dysfunction (increased acetylcholinesterase activity), brain inflammation, brain oxidative stress (reduction in brain superoxide dismutase, glutathione and catalase with an increase in thiobarbituric acid reactive substance level), with increased brain infarct size (2,3,5-triphenylterazolium chloride staining). The administration of montelukast considerably attenuated CCH induced cognitive impairments, cholinergic dysfunction, brain inflammation, brain oxidative stress as well as brain damage. Conclusions: The results of this study suggest that CCH has induced VaD in animals, which was attenuated by the treatment with montelukast, a specific modulator of CysLT1receptors. This is the first study which reports the utility of montelukast in experimental VaD. Future research should be targeted towards identification of various possible mechanisms of CysLT1receptor modulators in VaD and associated conditions.

Biography

Email: drbhupeshresearch@gmail.com bsharma5@amity.edu