Exacerbation of traumatically induced axonal injury by rapid posthypothermic rewarming and attenuation of axonal change by cyclosporin A

Object. Although considerable attention has been focused on the use of post traumatic hypothermia, little consideration has been given to the issue of posthypothermic rewarming and its potentially damaging consequences. In thi s communication, the authors examine the issue of rapid posthypothermic rew arming compared with gradual rewarming while exploring the potential utilit y of cyclosporin A (CsA) administration for attenuatings any rapid rewarmin g-induced axonal change. Methods. Male Sprague-Dawley rats were subjected to impact-acceleration inj ury and then their body temperature was lowered to 32 degreesC for 1 hour p ostinjury. After hypothermia, rewarming to normothermic levels was accompli shed either within a 20-minute period (rapid rewarming) or over a 90-minute period (slow rewarming). Some animals in the rapid rewarming group receive d intrathecal infusion of either CsA or its vehicle, whereas the rats in th e slow rewarming group received vehicle alone. Both the CsA and its vehicle were administered immediately before initiation of rewarming. Twenty-four hours postinjury the animals' brains were processed for visualization of am yloid precursor protein (APP), a marker of traumatic axonal injury. The APP -positive axonal density in the gradual ly rewarmed group receiving vehicle was statistically significantly reduced in comparison with the rapidly rew armed, vehicle-treated group. For the group undergoing rapid rewarming and treatment with CsA, a statistically significant reduction was also found in the density of the APP profiles compared with the rapidly rewarmed, vehicl e-treated group. Conclusions. The results of this study show that rapid rewarming exacerbate s traumatically induced axonal injury, which can be significantly attenuate d by administering CsA.