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 multipoten tial trophic effects on central nervous system cells, including neuron s, glia, and endothelial cells. In particular, it promotes the surviva l of a wide variety of brain neurons in vitro, and protects these neur ons against the effects of several neurotoxins, including excitatory a mino acids, hypoglycemia, and calcium ionophore. Since lack of substra te delivery, excitatory amino acid toxicity; and calcium entry into ce lls appear to be important processes in neuronal death after ischemia, we tested the hypothesis that: pretreatment with basic fibroblast gro wth fatter limits infarct Size in a model of focal cerebral ischemia i n vivo. Mature male Long-Evans rats received either continuous intrave ntricular infusion of basic fibroblast growth factor (1.2 mu g/day; wi th or without heparin, added to stabilize the growth factor) or vehicl e alone for 3 days before focal ischemic infarcts were made in the rig ht lateral cerebral cortex by permanent distal middle cerebral artery occlusion and temporary (45-minute) bilateral carotid occlusion. Intra operative measurements of core temperature, arterial blood pressure an d blood gases, blood glucose concentration, and hematocrit and postope rative measurements of temperature revealed no differences among vehic le- 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 imag e analysis. Overall, we found a 25% reduction in infarct volume in bas ic fibroblast growth factor- (N = 25) versus vehicle-treated (N = 23) animals (P < 0.01). This reduction was riot enhanced by the addition o f heparin. These data show that pretreatment with intraventricular bas ic fibroblast growth factor limits infarct size following focal cerebr al ischemia in rats.