GLUTAMATE RELEASE AND FREE-RADICAL PRODUCTION FOLLOWING BRAIN INJURY - EFFECTS OF POSTTRAUMATIC HYPOTHERMIA

Posttraumatic hypothermia reduces the extent of neuronal damage in rem ote cortical and subcortical structures following traumatic brain inju ry (TBI). We evaluated whether excessive extracellular release of glut amate and generation of hydroxyl radicals are associated with remote t raumatic injury, and whether posttraumatic hypothermia modulates these processes, Lateral fluid percussion was used to induce TBI in rats. T he salicylate-trapping method was used in conjunction with microdialys is and HPLC to detect hydroxyl radicals by measurement of the stable a dducts 2,3- and 2,5-dihydroxybenzoic acid (DHBA). Extracellular glutam ate was measured from the same samples, Following trauma, brain temper ature was maintained for 3 h at either 37 or 30 degrees C. Sham-trauma animals were treated in an identical manner. In the normothermic grou p, TBI induced significant elevations in 2,3-DHBA (3.3-fold, p < 0.01) , 2,5-DHBA (2.5-fold, p < 0.01), and glutamate (2.8-fold, p < 0.01) co mpared with controls. The levels of 2,3-DHBA and glutamate remained hi gh for approximately 1 h after trauma, whereas levels of 2,5-DHBA rema ined high for the entire sampling period (4 h). Linear regression anal ysis revealed a significant positive correlation between integrated 2, 3-DHBA and glutamate concentrations (p < 0.05). Posttraumatic hypother mia resulted in suppression of both 2,3- and 2,5-DHBA elevations and g lutamate release. The present data indicate that TBI is followed by pr ompt increases in both glutamate release and hydroxyl radical producti on from cortical regions adjacent to the impact site. The magnitude of glutamate release is correlated with the extent of the hydroxyl radic al adduct, raising the possibility that the two responses are associat ed. Posttraumatic hypothermia blunts both responses, suggesting a mech anism by which hypothermia confers protection following TBI.