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 determine whether evidence for severe ischemia (i.e., mean lCBF < 0.25 ml/g/min) could be demonstrated after severe brain injury. In addition, patterns of indium-labeled platelet accumulation and histopathological outcome were correlated with the hemodynamic alterations. METHODS: Sprague-Dawley rats (n = 23), anesthetized with halothane and maintained on a 70:30 mixture of nitrous oxide:oxygen and 0.5% halothane, underwent normothermic (37 degrees C) parasagittal fluid percussion brain injury (2.4-2.6 atm). Indium-111-tropolone-labeled platelets were injected 30 minutes before traumatic brain injury (TBI), while C-14-iodoantipyrine was infused 30 minutes after trauma for lCBF determination. Sham-operated animals (n = 8) underwent similar surgical procedures but were 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 that was most pronounced overlying the pial surface was commonly associated with severe reductions in lCBF within underlying cortical regions 30 minutes after TBI. For example, within the lateral parietal cortex, lCBF was significantly reduced from 1.67 +/- 0.11 ml/g per minute (mean +/- 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 focal severe ischemia, moderate reductions in lCBF were detected throughout the traumatized hemisphere, including the frontal and occipital cortices, hippocampus, thalamus, and striatum. Mild decreases in lCBF were also observed throughout the contralateral cerebral cortex. At 3 days after severe TBI, histopathology demonstrated intracerebral and subarachnoid hemorrhage associated with cerebral contusion and selective neuronal necrosis. CONCLUSION: These data indicate that multiple cerebrovascular abnormalities, including subarachnoid hemorrhage, focal platelet accumulation, and severe ischemia, are important early events in the pathogenesis of cortical contusion formation after TBI. Injury severity is expected to be a critical factor in determining what therapeutic strategies are attempted in the clinical setting.