PRETREATMENT WITH INTRAVENTRICULAR BASIC FIBROBLAST GROWTH-FACTOR DECREASES INFARCT SIZE FOLLOWING FOCAL CEREBRAL-ISCHEMIA IN RATS

Basic fibroblast growth factor is a polypeptide with potent multipotential trophic effects on central nervous system cells, including neurons, glia, and endothelial cells. In particular, it promotes the survival of a wide variety of brain neurons in vitro, and protects these neurons against the effects of several neurotoxins, including excitatory amino acids, hypoglycemia, and calcium ionophore. Since lack of substrate delivery, excitatory amino acid toxicity; and calcium entry into cells appear to be important processes in neuronal death after ischemia, we tested the hypothesis that: pretreatment with basic fibroblast growth fatter limits infarct Size in a model of focal cerebral ischemia in vivo. Mature male Long-Evans rats received either continuous intraventricular infusion of basic fibroblast growth factor (1.2 mu g/day; with or without heparin, added to stabilize the growth factor) or vehicle alone for 3 days before focal ischemic infarcts were made in the right lateral cerebral cortex by permanent distal middle cerebral artery occlusion and temporary (45-minute) bilateral carotid occlusion. Intraoperative measurements of core temperature, arterial blood pressure and blood gases, blood glucose concentration, and hematocrit and postoperative measurements of temperature revealed no differences among vehicle- versus basic fibroblast growth factor-treated animals: Twenty-four hours later, animals were killed, brains were removed and stained to visualize cortical infarcts, and infarct volume was determined by image analysis. Overall, we found a 25% reduction in infarct volume in basic fibroblast growth factor- (N = 25) versus vehicle-treated (N = 23) animals (P < 0.01). This reduction was riot enhanced by the addition of heparin. These data show that pretreatment with intraventricular basic fibroblast growth factor limits infarct size following focal cerebral ischemia in rats.