POSTTRAUMATIC CEREBRAL-ISCHEMIA AFTER FLUID PERCUSSION BRAIN INJURY -AN AUTORADIOGRAPHIC AND HISTOPATHOLOGICAL STUDY IN RATS

OBJECTIVES: Mild-to-moderate reductions in local cerebral blood flow ( lCBF) have been reported to occur in rats after moderate (1.7-2.2 atm) fluid percussion brain injury. The purpose of this study was to deter mine whether evidence for severe ischemia (i.e., mean lCBF < 0.25 ml/g /min) could be demonstrated after severe brain injury. In addition, pa tterns of indium-labeled platelet accumulation and histopathological o utcome were correlated with the hemodynamic alterations. METHODS: Spra gue-Dawley rats (n = 23), anesthetized with halothane and maintained o n a 70:30 mixture of nitrous oxide:oxygen and 0.5% halothane, underwen t normothermic (37 degrees C) parasagittal fluid percussion brain inju ry (2.4-2.6 atm). Indium-111-tropolone-labeled platelets were injected 30 minutes before traumatic brain injury (TBI), while C-14-iodoantipy rine was infused 30 minutes after trauma for lCBF determination. Sham- operated animals (n = 8) underwent similar surgical procedures but wer e not injured. For histopathological analysis, traumatized rats (n = 5 ) were perfusion-fixed 3 days after TBI. RESULTS: In autoradiographic images of indium-labeled platelets, abnormal platelet accumulation tha t was most pronounced overlying the pial surface was commonly associat ed with severe reductions in lCBF within underlying cortical regions 3 0 minutes after TBI. For example, within the lateral parietal cortex, lCBF was significantly reduced from 1.67 +/- 0.11 ml/g per minute (mea n +/- standard error of the mean) in sham-operated animals to 0.23 +/- 0.03 ml/g per minute within the traumatized group. In addition to foc al severe ischemia, moderate reductions in lCBF were detected througho ut the traumatized hemisphere, including the frontal and occipital cor tices, hippocampus, thalamus, and striatum. Mild decreases in lCBF wer e also observed throughout the contralateral cerebral cortex. At 3 day s after severe TBI, histopathology demonstrated intracerebral and suba rachnoid hemorrhage associated with cerebral contusion and selective n euronal necrosis. CONCLUSION: These data indicate that multiple cerebr ovascular abnormalities, including subarachnoid hemorrhage, focal plat elet accumulation, and severe ischemia, are important early events in the pathogenesis of cortical contusion formation after TBI. Injury sev erity is expected to be a critical factor in determining what therapeu tic strategies are attempted in the clinical setting.