Postischemic administration of basic fibroblast growth factor improves sensorimotor function and reduces infarct size following permanent focal cerebral ischemia in the rat.
Basic fibroblast growth factor (bFGF) is a polypeptide with potent trophic and protective effects on the brain. bFGF has been reported to exert neuroprotection against a wide variety of insults, including ischemic neuronal injury. To date, animal models of focal ischemia have not been translated to efficacy in stroke clinically with respect to testing of neuroprotective agents. Because functional outcome is the measurement of efficacy for putative neuroprotective agents in the clinic, we sought to evaluate the functional consequences of bFGF administration in rats subjected to focal ischemia. In this study, we assessed the effects of bFGF on functional outcome as well as infarct size in rats subjected to severe cerebral ischemia by permanent occlusion of the middle cerebral artery (MCAO). Male Sprague-Dawley rats were subjected to permanent MCAO by the intraluminal filament technique. Two hours following occlusion, rats were infused intravenously with either bFGF, at a dose of 150 microg/kg, or vehicle alone. Functional sensorimotor impairment, which was assessed by the accelerating rotarod test, was recorded at baseline and compared to performance assessed at 24 h after MCAO. Permanent occlusion of the MCA caused marked impairment in rotarod performance in both groups. Treatment of rats with bFGF showed a significant 46% improvement in rotarod fall latency when compared with that from the animals treated with vehicle alone. The volume of cortical infarction was significantly reduced by 32% as a function of bFGF treatment. These results suggest that the delayed intravenous administration of bFGF improves sensorimotor function as well as reduces infarct size following permanent focal ischemia in rat.
Li
Qiu
Q
Department of Pharmacology, Pharmacia, Kalamazoo, Michigan 49001, USA.
Stephenson
Diane
D
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D002544:Cerebral Infarction / Q000473:pathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage*; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D007262:Infusions, Intravenous; D016014:Linear Models; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome
D018696:Neuroprotective Agents; D016222:Fibroblast Growth Factor 2