Basic fibroblast growth factor ameliorates focal ischemic injury by rcbf-independent mechanisms in enos mutant mice. Huang, Zhihong, Ke Chen, Paul L. Huang, Seth P. Finklestein, and Michael A. Moskowitz. Laboratory of Stroke and Neurovascular Regulation and CNS Growth Factor Research Laboratory, Department of Neurology; and Cardiovascular Research Center, Department of Medicine; Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129
APStracts 3:0465H, 1996.
Genetically-engineered mice deficient in the expression of type III NOS [endothelial nitric oxide synthase (eNOS)] were used to dissect the importance of nitric oxide (NO)-dependent augmentation of regional cerebral blood flow (rCBF) to infarct volume reduction following basic fibroblast growth factor (bFGF) infusion during acute middle cerebral artery (MCA) occlusion. We have shown previously that intravenously-administered bFGF reduces infarct volume following MCA occlusion in rats and that bFGF dilates cerebral pial arterioles by NO-dependent mechanisms. Halothane-anesthetized eNOS knockout and wild type mice were subjected to permanent MCA occlusion by intraluminal filament for 24 h. bFGF (100 [mu]g/kg/h) was infused intravenously for 2 h, beginning 15 min after the onset of occlusion. Infarct volume was reduced from 119 +/- 8 to 93 +/- 4 mm3 (22% reduction, p<0.05) or from 102 +/- 9 to 77 +/- 6 mm3 (24% reduction, p<0.05) in eNOS knockout or wild type mice respectively (means +/- SEM; N=10 per group), and neurological deficits were also significantly reduced. While bFGF infusion caused a 27% increase in rCBF and a 17% reduction in vascular resistance in the infarct margin of wild type animals as measured by laser doppler flowmetry, bFGF did not enhance rCBF in the infarct margin of eNOS mutant mice. These data indicate that intravenous bFGF reduces infarct volume following focal ischemia by mechanisms that are largely blood flow-independent. 

Received 12 July 1996; accepted in final form 18 September 1996.
APS Manuscript Number H620-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 13 November 1996