THE ROLE OF ACTIVATED NEUTROPHILS IN SECONDARY BRAIN INJURY

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The activation and accumulation of neutrophils in areas of tissue injury is being increasingly recognized as one potential source of deleterious pro- inflammatory activity which can extend or otherwise exacerbate the primary insult. This study is designed to investigate the impact of neutrophil modulation and a 21-aminosteroid on vasogenic and cytotoxic edema of traumatic brain injury. The proposal involves two acute animal models of lateralized hemispheric injury; a cryogenic lesion to model vasogenic edema, and a percussive lesion to model a combination of vasogenic and cytotoxic edema. The differential effects of the chloride/bicarbonate exchange blocker, L644,711, which inhibits neutrophil function and astrocyte swelling, anti-neutrophil antisera, which depletes neutrophils systematically and the lazaroid U78517F, an inhibitor of lipid peroxidation, will be determined in these two models as separate treatment paradigms. The parameters to be monitored, measured and contrasted to establish the differential impact of these treatments are intracranial pressure, cerebral blood flow, tissue infarct, hemispheric volume and water weight, the ratio of intracellular to extracellular space and the extent of neutrophil infiltration. The results of these studies may support neutrophil modulation as a novel strategy in the acute management of traumatic brain injury.