Importance of posttraumatic hypothermia and hyperthermia on the inflammatory response after fluid percussion brain injury: Biochemical and immunocytochemical studies

The purpose of this study was to investigate: 1) the temporal and regional profile of polymorphonuclear leukocyte (PMNL) infiltration after moderate t raumatic brain injury using the parasagittal fluid percussion model and 2) the effects of posttraumatic hypothermia (30 degrees C) and hyperthermia (3 4 degrees C) on the acute and subacute inflammatory response. We hypothesiz ed that posttraumatic hypothermia would reduce the degree of PMNL accumulat ion whereas hyperthermia would exacerbate this response to injury. In the f irst series of experiments we quantitated the temporal profile of altered m yeloperoxidase activity under normothermic (37 degrees C) conditions (n = 2 0). The rats were allowed to survive for 3 hours, 24 hours, 3 days, or 7 da ys after trauma, and brains were dissected into cortical and subcortical re gions ipsilateral and contralateral to injury. Additional animals were perf used and fixed for the immunocytochemical visualization of myeloperoxidase (n = 15). In the second series of experiments, rats (n = 25) were killed 3 hours or 3 days after the 3-hour monitoring period of normothermia (36.5 de grees C), hypothermia (30 degrees C), or hyperthemia (39 degrees C) (n = 4 to 5 per group), and myeloperoxidase activity was again quantitated. In nor mothermic rats, the enzymatic activity of myeloperoxidase was significantly increased (P < 0.05) at 3 hours within the anterior cortical segment (213. 97 +/- 56.2 versus control 65.5 +/- 52.3 U/g of wet tissue; mean +/- SD) an d posterior (injured) cortical and subcortical segments compared to sham-op erated rats (305.76 +/- 27.8 and 258.67 +/- 101.4 U/g of wet tissue versus control 62.8 +/- 24.8 and 37.28 1 35.6 U/g of wet tissue; P < 0.0001, P < 0 .05, respectively). At 24 hours and 7-days after trauma only the posterior cortical region (P < 0.005, P < 0.05, respectively) exhibited increased mye loperoxidase activity. However, 3 days after trauma, myeloperoxidase activi ty was also significantly increased within the anterior cortical segment (P < 0.05) and in posterior cortical and subcortical regions compared to sham -operated cortex (P < 0.0001, P < 0.05, respectively), Immunocytochemical a nalysis of myeloperoxidase reactivity at 3 hours, 24 hours, 3- and 7-days d emonstrated large numbers of immunoreactive leukocytes within and associate d with blood vessels, damaged tissues, and subarachnoid spaces. Posttraumat ic hypothermia and hyperthermia had significant effects on myeloperoxidase activity at both 3 hours and 3 days after traumatic brain injury. Posttraum atic hypothermia reduced myeloperoxidase activity in the injured and noninj ured cortical and subcortical segments compared to normothermic values (P < 0.05). In contrast, posttraumatic hyperthermia significantly elevated myel operoxidase activity in the posterior cortical region compared to normother mic values at both 3 hours and 3 days (473.5 +/- 258.4 and 100.11 +/- 27.58 U/g of wet tissue, respectively, P < 0.05 versus controls). These results indicate that posttraumatic hypothermia decreases early and more prolonged myeloperoxidase activation whereas hyperthermia increases myeloperoxidase a ctivity. Temperature-dependent alterations in PMNL accumulation appear to b e a potential mechanism by which posttraumatic temperature manipulations ma y influence traumatic outcome.