Delayed treatment with intravenous basic fibroblast growth factor reduces infarct size following permanent focal cerebral ischemia in rats.
Basic fibroblast growth factor (bFGF) is a polypeptide that supports the survival of brain cells (including neurons, glia, and endothelia) and protects neurons against a number of toxins and insults in vitro. This factor is also a potent dilator of cerebral pial arterioles in vivo. In previous studies, we found that intraventricularly administered bFGF reduced infarct volume in a model of focal cerebral ischemia in rats. In the current study, bFGF (45 micrograms/kg/h) in vehicle, or vehicle alone, was infused intravenously for 3 h, beginning at 30 min after permanent middle cerebral artery occlusion by intraluminal suture in mature Sprague-Dawley rats. After 24 h, neurological deficit (as assessed by a 0- to 5-point scale, with 5 = most severe) was 2.6 +/- 1.0 in vehicle-treated and 1.5 +/- 1.3 in bFGF-treated rats (mean +/- SD; N = 12 vs. 11; p = 0.009). Infarct volume was 297 +/- 65 mm3 in vehicle- and 143 +/- 135 mm3 in bFGF-treated animals (p = 0.002). During infusion, there was a modest decrease in mean arterial blood pressure but no changes in arterial blood gases or core or brain temperature in bFGF-treated rats. Autoradiography following intravenous administration of 111In-labeled bFGF showed that labeled bFGF crossed the damaged blood-brain barrier to enter the ischemic (but not the nonischemic) hemisphere. Whether the infarct-reducing effects of bFGF depend on intraparenchymal or intravascular mechanisms requires further study.
Fisher
M
M
Department of Neurology, Medical Center of Central Massachusetts, Worcester 01605, USA.
Meadows
M E
ME
Do
T
T
Weise
J
J
Trubetskoy
V
V
Charette
M
M
Finklestein
S P
SP
D000818:Animals; D001345:Autoradiography; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology*; D002544:Cerebral Infarction / Q000209:etiology / Q000473:pathology*; D016222:Fibroblast Growth Factor 2 / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007275:Injections, Intravenous; D008297:Male; D011233:Precipitin Tests; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D016222:Fibroblast Growth Factor 2