Posttreatment with Intravenous Basic Fibroblast Growth Factor Reduces Histopathological Damage Following Fluid-Percussion Brain Injury in Rats

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Abstract
The purpose of this study was to determine whether treatment with intravenous basic fibroblast growth factor (bFGF) would protect histopathologically in a rat model of traumatic brain injury (TBI). Twenty-four hours prior to TBI, the fluid-percussion interface was positioned parasagittally over the right cerebral cortex. On the second day, fasted rats were anesthetized with 70% nitrous oxide, 1% halothane, and 30% oxygen. Under controlled physiological conditions and normothermic brain temperature (37–37.5°C), rats were injured with a fluid-percussion pulse ranging from 1.6 to 1.9 atm. Rats were randomized into two groups where either bFGF (45 μg/kg/h) in vehicle (n = 7) or vehicle alone (n = 7) was infused intravenously for 3 h, beginning 30 min after TBI. Three days later, brains were perfusion-fixed for histopathological assessment and quantitative analysis of contusion volume and numbers of necrotic cortical neurons. In vehicle-treated animals, necrotic neurons were observed throughout the lateral cerebral cortex remote from the impact site. In addition, an intracerebral contusion was present in all rats at the gray-white interface underlying the injured cortical areas. Posttraumatic administration of bFGF significantly reduced the numbers of damaged cortical neuron profiles at several coronal levels and reduced the total number of damaged neurons (696 ± 148 vs. 1,248 ± 198, means ± SEM), p < 0.05, ANOVA). In addition, contusion areas at several coronal levels as well as total contusion volume was significantly reduced (1.13 ± 0.39 mm3 vs. 3.18 ± 0.81 mm3,p < 0.05). These data demonstrate neuroprotection with intravenous bFGF infusion in the posttraumatic setting.