Exacerbation of traumatically induced axonal injury by rapid posthypothermic rewarming and attenuation of axonal change by cyclosporin A.
OBJECTIVE
Although considerable attention has been focused on the use of posttraumatic hypothermia, little consideration has been given to the issue of posthypothermic rewarming and its potentially damaging consequences. In this communication, the authors examine the issue of rapid posthypothermic rewarming compared with gradual rewarming while exploring the potential utility of cyclosporin A (CsA) administration for attenuating any rapid rewarming-induced axonal change.


METHODS
Male Sprague-Dawley rats were subjected to impact-acceleration injury and then their body temperature was lowered to 32 degrees C for 1 hour postinjury. After hypothermia, rewarming to normothermic levels was accomplished either within a 20-minute period (rapid rewarming) or over a 90-minute period (slow rewarming). Some animals in the rapid rewarming group received intrathecal infusion of either CsA or its vehicle, whereas the rats in the 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 amyloid precursor protein (APP), a marker of traumatic axonal injury. The APP-positive axonal density in the gradually rewarmed group receiving vehicle was statistically significantly reduced in comparison with the rapidly rewarmed, 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, vehicle-treated group.


CONCLUSIONS
The results of this study show that rapid rewarming exacerbates traumatically induced axonal injury, which can be significantly attenuated by administering CsA.
Suehiro
E
E
Department of Anatomy, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0709, USA.
Povlishock
J T
JT
D016564:Amyloid beta-Protein Precursor / Q000032:analysis; D000818:Animals; D001369:Axons / Q000737:chemistry / Q000187:drug effects / Q000473:pathology*; D001831:Body Temperature; D001930:Brain Injuries / Q000188:drug therapy* / Q000473:pathology*; D016572:Cyclosporine / Q000494:pharmacology*; D007036:Hypothermia, Induced / Q000009:adverse effects* / Q000379:methods; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D016564:Amyloid beta-Protein Precursor; D007166:Immunosuppressive Agents; D016572:Cyclosporine