title: Neuroprotective Effects of Agomelatine and Vinpocetine Against Chronic Cerebral Hypoperfusion Induced Vascular Dementia.
abstract: Chronic cerebral hypoperfusion (CCH) has been considered as a critical cause for the development of cognitive decline and dementia of vascular origin. Melatonin receptors have been reported to be beneficial in improving memory deterioration. Phosphodiesterase-1 (PDE1) enzyme offers protection against cognitive impairments and cerebrovascular disorders. Aim of this study is to explore the role of agomelatine (a dual MT1 and MT2 melatonin receptor agonist) and vinpocetine (selective PDE1 inhibitor) in CCH induced vascular dementia (VaD). Two vessel occlusion (2VO) or bilateral common carotid arteries ligation method was performed to initiate a phase of chronic hypoperfusion in mice. 2VO animals have shown significant cognitive deficits (Morris water maze), cholinergic dysfunction (increased acetyl cholinesterase -AChE) activity alongwith increased brain oxidative stress (decreased brain catalase, glutathione, as well as superoxide dismutase with an increase in malondialdehyde levels), and significant increase in brain infarct size (2,3,5- triphenylterazolium chloride-TTC staining). Treatment of agomelatine and vinpocetine reduced CCH induced learning and memory deficits and limited cholinergic dysfunction, oxidative stress, and tissue damage, suggesting that agomelatine and vinpocetine may provide benefits in CCH induced VaD.
authors.forename: Surbhi
authors.initials: S
authors.lastname: Gupta
authors.forename: Prabhat
authors.initials: P
authors.lastname: Singh
authors.forename: Brij Mohan
authors.initials: BM
authors.lastname: Sharma
authors.affiliation: Department of Pharmacology, School of Pharmacy, Bharat Institute of Technology, Partapur Bypass, Meerut, Uttar Pradesh, India. drbhupeshresearch@gmail.com.
authors.forename: Bhupesh
authors.initials: B
authors.lastname: Sharma
mesh_terms: D000081:Acetamides / Q000627:therapeutic use*; D000110:Acetylcholinesterase / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D001157:Arterial Occlusive Diseases / Q000150:complications; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D015140:Dementia, Vascular / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors; D014748:Vinca Alkaloids / Q000627:therapeutic use*; D009281:Naphthalenes
chemical_list: D000081:Acetamides; D000110:Acetylcholinesterase; D002374:Catalase; D005978:Glutathione; D008315:Malondialdehyde; D018696:Neuroprotective Agents; D013482:Superoxide Dismutase; D014748:Vinca Alkaloids; C084711:agomelatine; D009281:Naphthalenes; C013983:vinpocetine