Nimodipine attenuates biochemical, behavioral and histopathological alterations induced by acute transient and long-term bilateral common carotid occlusion in rats.
Restoration of blood flow to an ischemic brain region is associated with generation of reactive oxygen species with consequent reperfusion injury. Chronic cerebral hypoperfusion induced by permanent occlusion of bilateral common carotid arteries in rats is associated with behavioral and histopathological alterations. Nimodipine, a dihydropyridine calcium channel antagonist, has potent vasodilatory effect on cerebral vessels and increases cerebral blood flow. We analyzed whether nimodipine reduces injury caused by transient forebrain ischemia and long-term cerebral hypoperfusion. Bilateral common carotid occlusion for 30 min followed by 45 min reperfusion resulted in a two-fold increase in lipid peroxidation and superoxide dismutase activity. Nimodipine pretreatment (4 mg/kg, i.p.) brought down these levels by 30 and 23%, respectively. Long-term cerebral hypoperfusion in rats caused a propensity towards anxiety and listlessness (open field paradigm) accompanied by deficits of learning and memory (Morris' water maze testing). Additionally, histopathological observation in hypoperfused brains revealed reactive changes in the form of perivascular inflammation, gliosis and astrocytosis. Nimodipine treatment significantly alleviated these changes in behavioral and histopathological parameters. Our data confirm the protective role of nimodipine in ischemia reperfusion injury. Moreover, it suggests the beneficial role of nimodipine in cerebrovascular insufficiency states and dementia.
Yanpallewar
S U
SU
Department of Pharmacology, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221 005, India.
Hota
Debashish
D
Rai
Sunita
S
Kumar
Mohan
M
Acharya
S B
SB
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology; D017536:Carotid Artery, Common; D016893:Carotid Stenosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002560:Cerebrovascular Circulation; D004924:Escape Reaction / Q000187:drug effects; D005260:Female; D015227:Lipid Peroxidation; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects; D009553:Nimodipine / Q000494:pharmacology* / Q000627:therapeutic use; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D015427:Reperfusion Injury / Q000188:drug therapy*; D013482:Superoxide Dismutase / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology* / Q000627:therapeutic use
D014665:Vasodilator Agents; D008315:Malondialdehyde; D009553:Nimodipine; D013482:Superoxide Dismutase