Investigation of the role of pharmacological modulation of adrenergic receptors in experimental vascular dementia

Abstract

Investigation of the Role of Pharmacological Modulation of Adrenergic Receptors in Experimental Vascular Dementia newlineBrijmohan Sharma newlineABSTRACT newlineIntroduction: Cerebrovascular and cardiovascular diseases are considered major age-related risk factors leading to reduced brain perfusion, causing hypoxia and neuronal disorders which are involved in the development of vascular dementia (VaD). A latest report on dementia indicates around 5.3 millions cases in India out of which approximately 40% cases reported with VaD. newlineAim: This investigation has been structured to explore the outcomes of nicergoline and nebivolol in 2-kidney-1-clip (2K1C), pancreatectomy (PAN), and ovariectomy (OVX) provoked vascular endothelium dysfunction and related dementia. newlineMethodology: 2K1C was employed to provoke renovascular hypertension in Albino Wistar rats, similarly partial PAN was performed to provoke diabetes and bilateral OVX was performed to provoke estrogen deficit in female rats. Hypertension, diabetes, and estrogen deficit models were employed to provoke VaD. Mean arterial blood pressure, serum glucose, and serum estradiol levels were assessed to confirm the effectiveness of models employed to provoke hypertension, diabetes, and estradiol deficit respectively. All the abnormalities lead to endothelial dysfunctions, learning and memory decline, and associated dementia. Morris water maze (MWM), elevated plus maze (EPM), and attentional set-shifting tests (ASST) were used to assess spatial learning, memory, reversal learning, and executive functioning in animals. Endothelium dysfunctions were assessed by evaluating vascular endothelium dependant and independent relaxation using aortic ring preparation. Other parameters include serum nitrite/nitrate, aortic superoxide anion, brain s oxidative markers (thiobarbituric acid reactive species-TBARS, reduced glutathione-GSH, superoxide dismutase-SOD, and catalase-CAT), inflammatory markers (myeloperoxidase-MPO), acetylcholinesterase-AChE activitywere also assessed. Histopathological examination o