Effect of aminoguanidine on post-ischemic damage in rodent model of stroke.
A number of studies have shown that aminoguanidine (AG) has neuroprotective effect in chronic phase of cerebral ischemia. However, dose dependent effects of AG on acute phase of ischemic-reperfusion injuries, as well as neurological dysfunctions are not completely clear. Transient focal cerebral ischemia was induced in rats by 60 min middle cerebral artery occlusion (MCAO), followed by 23 h reperfusion. Saline as vehicle or AG at doses 75, 150, or 300 mg/kg ip was administered at the beginning of ischemia. Infarct volume and motor dysfunction were assessed 24 h after MCAO. Treatment with AG at dose 75, 150, or 300 mg/kg ip significantly reduces total infarct volumes by 44%, 56% and 36%, respectively. In addition, AG only at dose 150 significantly improves neurological dysfunction in comparison with saline group. Our findings show that AG decrease ischemic brain damage dose-dependently and improve neurological recovery in acute phase of transient focal cerebral ischemia. More studies are needed to find therapeutic window and mechanisms of neuroprotection of AG in early phase of cerebral ischemia.
Vakili
Abedin
A
Laboratory of Cerebrovascular Research, Department and Research Center of Physiology, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran. abvakili@yahoo.com
Zahedi-Khorasani
Mahdi
M
D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006146:Guanidines / Q000627:therapeutic use*; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D020521:Stroke / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology
D006146:Guanidines; D018696:Neuroprotective Agents; D019001:Nitric Oxide Synthase; C004479:pimagedine