Effect of alpha-phenyl-N-tert-butylnitrone on brain cell membrane functionand energy metabolism in experimental Escherichia coli meningitis in the newborn piglet

We evaluated the efficacy of alpha-phenyl-N-tert-butylnitrone as an adjunct ive therapy in experimental bacterial meningitis in the newborn piglet. Men ingitis was induced:by intracisternal injection of 10(8) colony-forming uni ts of Escherichia coli in 100 mu l of saline. alpha-Phenyl-N-tert-butylnitr one 100 mg/kg was given as a bolus intravenous injection 30 min before indu ction of meningitis. Although it completely abolished the elevated CSF tumo r necrosis factor-alpha level observed in the meningitis group, alpha-pheny l-N-tert-butylnitrone did not down-modulate parameters of inflammatory resp onses such as increased intracranial pressure, hypoglycorrhachia, elevated CSF lactate level, and CSF leukocytosis observed in this group. However, al pha-phenyl-N-tert-butylnitrone treatment mitigated alterations in brain cel l membrane structure and function during meningitis, evidenced by ameliorat ion of increased brain cell membrane lipid peroxidation products (conjugate d dienes) and decreased Na+,K+-ATPase activity. Reduced mean arterial blood pressure, cerebral perfusion pressure, brain glucose concentration, and ce rebral energy stores and marginally increased brain lactate level observed in the meningitis group were also ameliorated. These results suggest that a lthough it failed to attenuate the inflammatory responses, alpha-phenyl-N-t ert-butylnitrone was effective in ameliorating brain injury in neonatal bac terial meningitis.