DELAYED POSTTRAUMATIC BRAIN HYPERTHERMIA WORSENS OUTCOME AFTER FLUID PERCUSSION BRAIN INJURY - A LIGHT AND ELECTRON-MICROSCOPIC STUDY IN RATS

THE MORPHOLOGICAL CONSEQUENCES of delayed posttraumatic brain hyperthe rmia (39 degrees C) after fluid percussion brain injury were assessed in rats. Sprague-Dawley rats anesthetized with 4% halothane and mainta ined on a 70:30 mixture of nitrous oxide:oxygen and 0.5% halothane und erwent moderate (1.5-2.0 atm) traumatic brain injury with the injury s crew positioned parasagittally over the right parieto-occipital cortex . At 24 hours after traumatic brain injury, the rats were reanesthetiz ed and randomized into two groups in which either a 3-hour period of b rain normothermia (36.5 degrees C, n = 18) or hyperthermia (39 degrees C, n = 18) was maintained. Sham-operated controls (n = 10) underwent all surgical and temperature-monitoring procedures. After the 3-hour m onitoring period, the rats were allowed to survive for 3 days for ligh t microscopic analysis or were injected with the protein tracer horser adish peroxidase and were perfusion-fixed 15 minutes later for light a nd electron microscopic analysis. At 4 days after traumatic brain inju ry, delayed posttraumatic hyperthermia (n = 12) significantly increase d mortality (47%) and contusion volume (1.7 +/- 0.69 mm(3), mean a sta ndard error of the mean), compared to normothermia (n = 12) (18% morta lity and 0.13 +/- 0.21 mm(3) contusion volume) (P < 0.01, analysis of variance). At 15 minutes after the 3-hour hyperthermic period, the are a of hemorrhage and horseradish peroxidase extravasation overlying the lateral external capsule was significantly increased (2.52 +/- 0.71 m m(2), mean a standard error of the mean, versus 0.43 +/- 0.16 mm(2)) ( P < 0.01), compared to normothermic rats. Examination of toluidine blu e-stained plastic sections demonstrated a higher frequency of abnormal ly swollen myelinated axons per high microscopic field with hypertherm ia. For example, numbers of swollen axons within the sixth layer of th e right somatosensory cortex, corpus callosum, and internal capsule we re 7.3 +/- 1.3, 4.2 +/- 1.4, and 3.0 +/- 1.2 axons (mean +/- standard error of the mean) with normothermia, respectively, compared with 24.7 +/- 12.1, 33.1 +/- 4.2, and 27.3 +/- 3.1 axons with hyperthermia resp ectively (P < 0.01). An ultrastructural examination of the swollen axo ns demonstrated a severely thinned myelin sheath containing axoplasm d evoid of cytoskeletal components. These experimental results indicate that posttraumatic brain hyperthermia might increase morbidity and mor tality in patients with head injury by aggravating axonal and microvas cular damage.