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 (16- desmethyl-tirilazad) on the concentration of extracellular superoxide anion following fluid percussion traumatic brain injury (TBI) measured by a cytochrome c-coated electrode and on local cerebral perfusion (CBF(Id)) measured by laser Doppler flowmetry (LDF). U-74389G in a dose of 3 mg/kg reduced superoxide anion concentrations 60 min after TBI significantly but had no significant effect on CBF(Id). These results indicate that reduction of CBF after TBI can be dissociated from superoxide anion production. Persistent ischemia may limit neuroprotection efficacy and may contribute to divergent outcome results in clinical and animal trials using agents to modify reactive oxygen species.