THE 21-AMINOSTEROID U-74389G REDUCES CEREBRAL SUPEROXIDE ANION CONCENTRATION FOLLOWING FLUID PERCUSSION INJURY OF THE BRAIN

We examined the effects of the 21-aminosteroid antioxidant U-74389G (1 6-desmethyl-tirilazad) on the concentration of extracellular superoxid e anion following fluid percussion traumatic brain injury (TBI) measur ed by a cytochrome c-coated electrode and on local cerebral perfusion (CBFld) measured by laser Doppler flowmetry (LDF). U-74389G in a dose of 3 mg/kg reduced superoxide anion concentrations 60 min after TBI si gnificantly but had no significant effect on CBFld. These results indi cate that reduction of CBF after TBI can be dissociated from superoxid e anion production. Persistent ischemia may limit neuroprotection effi cacy and may contribute to divergent outcome results in clinical and a nimal trials using agents to modify reactive oxygen species.