POSTTREATMENT WITH INTRAVENOUS BASIC FIBROBLAST GROWTH-FACTOR REDUCESHISTOPATHOLOGICAL DAMAGE FOLLOWING FLUID-PERCUSSION BRAIN INJURY IN RATS

The purpose of this study was to determine whether treatment with intr avenous basic fibroblast growth factor (bFGF) would protect histopatho logically in a rat model of traumatic brain injury (TBI). Twenty-four hours prior to TBI, the fluid-percussion interface was positioned para sagittally over the right cerebral cortex. On the second day, fasted r ats were anesthetized with 70% nitrous oxide, 1% halothane, and 30% ox ygen. Under controlled physiological conditions and normothermic brain temperature (37-37.5 degrees C), rats were injured with a fluid-percu ssion pulse ranging from 1.6 to 1.9 atm. Rats were randomized into two groups where either bFGF (45 mu g/kg/h) in vehicle (n = 7) or vehicle alone (n = 7) was infused intravenously for 3 h, beginning 30 min aft er TBI. Three days later, brains were perfusion-fixed for histopatholo gical assessment and quantitative analysis of contusion volume and num bers of necrotic cortical neurons. In vehicle-treated animals, necroti c neurons were observed throughout the lateral cerebral cortex remote from the impact site. In addition, an intracerebral contusion was pres ent in all rats at the gray-white interface underlying the injured cor tical areas. Posttraumatic administration of bFGF significantly reduce d the numbers of damaged cortical neuron profiles at several coronal l evels and reduced the total number of damaged neurons (696 +/- 148 vs. 1,248 +/- 198, means +/- SEM), p < 0.05, ANOVA). In addition, contusi on areas at several coronal levels as well as total contusion volume w as significantly reduced (1.13 +/- 0.39 mm(3) vs. 3.18 +/- 0.81 mm(3), p < 0.05). These data demonstrate neuroprotection with intravenous bF GF infusion in the posttraumatic setting.