title: Investigation of the role of non-selective calcium channel blocker (flunarizine) on cerebral ischemic-reperfusion associated cognitive dysfunction in aged mice.
abstract: The present study was designed to investigate the role of flunarizine (a non-selective calcium channel blocker) on cerebral ischemic-reperfusion associated cognitive dysfunction in aged mice. Bilateral carotid artery occlusion of 12min followed by reperfusion for 24h was given to induce cerebral injury in male Swiss mice. The assessment of learning & memory was performed by Morris water maze test; motor in-coordination was evaluated by rota rod, lateral push and inclined beam walking tests; cerebral infarct size was quantified by triphenyltetrazolium chloride staining. In addition, reduced glutathione (GSH), total calcium and acetylcholinesterase (AChE) activity were also estimated in aged brain tissue. Donepezil treated group served as a positive control in this study. Ischemia reperfusion (I/R) injury produced significant increase in cerebral infarct size. A significant loss of memory along with impairment of motor performance was also noted. Further, I/R injury also produced significant increase in levels of total calcium, AChE activity and decrease in GSH levels. Pretreatment of flunarizine significantly attenuated I/R induced infarct size, behavioral and biochemical changes. Hence, it may be concluded that, a non-selective calcium channel blocker can be useful in I/R associated cognitive dysfunction due to its anti-oxidant, anti-infarct and modulatory actions of neurotransmitters & calcium channels.
authors: Department of Pharmaceutical Sciences & Drug Research, Punjabi University, Patiala 147002, Punjab, India.
authors: Puja
authors: P
authors: Gulati
authors: Department of Pharmaceutical Sciences & Drug Research, Punjabi University, Patiala 147002, Punjab, India; Department of Pharmacology, Neuropharmacology Division, Akal Pharmacology & Toxicology Research Centre, Akal College of Pharmacy & Technical Education (ACPTE), Masuana Sahib, Sangrur 148001, Punjab, India. Electronic address: arunachalammu@gmail.com.
authors: Arunachalam
authors: A
authors: Muthuraman
authors: Department of Pharmacology, Neuropharmacology Division, Akal Pharmacology & Toxicology Research Centre, Akal College of Pharmacy & Technical Education (ACPTE), Masuana Sahib, Sangrur 148001, Punjab, India.
authors: Parneet
authors: P
authors: Kaur
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000375:Aging; D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy; D002121:Calcium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D003072:Cognition Disorders / Q000188:drug therapy*; D005444:Flunarizine / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D015427:Reperfusion Injury / Q000188:drug therapy*
chemical_list: D002121:Calcium Channel Blockers; D000110:Acetylcholinesterase; D005444:Flunarizine
keywords: Flunarizine; Inclined beam test; Ischemia–reperfusion injury; Lateral push test; Morris water-maze; Reduced glutathione