Delayed intravenous administration of basic fibroblast growth factor (bFGF) reduces infarct volume in a model of focal cerebral ischemia/reperfusion in the rat.
Basic fibroblast growth factor (bFGF) is a potent neurotrophic and vasoactive peptide. Previous studies have shown that intraventricularly-administered bFGF reduces the size of cerebral infarcts following focal ischemia. In the current study, we tested the effects of intravenously-administered bFGF in a model of focal ischemia/reperfusion. The right middle cerebral artery of mature male Wistar rats was occluded by intraluminal suture. After 2 h of occlusion, the suture was removed and intravenous infusion of bFGF in vehicle (45 micrograms/kg/h) or vehicle alone was begun, lasting 3 h. Animals were weighed and evaluated neurologically until sacrifice 7 days after ischemia. The volume of cerebral infarcts was then determined by H and E staining and image analysis. We found a 40% reduction in infarct volume in bFGF- vs. vehicle-treated rats (n = 11 vs. 11, P < 0.05). Reduction in infarct volume was associated with improved neurological outcome and regained body weight in bFGF-treated animals (both P < 0.05). No change in blood pressure was found during bFGF treatment. These results show that the delayed intravenous administration of bFGF reduces infarct size in this model of focal ischemia/reperfusion. The mechanisms of infarct reduction may include direct cytoprotective and/or vasoactive effects.
Jiang
N
N
Department of Neurology, Henry Ford Hospital, Detroit, MI, USA.
Finklestein
S P
SP
Do
T
T
Caday
C G
CG
Charette
M
M
Chopp
M
M
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000473:pathology; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D002544:Cerebral Infarction / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004334:Drug Administration Schedule; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage / Q000627:therapeutic use*; D007091:Image Processing, Computer-Assisted; D007262:Infusions, Intravenous; D008297:Male; D009474:Neurons / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*
D016222:Fibroblast Growth Factor 2