Effect of α-Phenyl-N-tert-Butylnitrone on Brain Cell Membrane Function and Energy Metabolism in Experimental Escherichia coli Meningitis in the Newborn Piglet

Abstract

We evaluated the efficacy of alpha-phenyl-N-tertbutylnitrone as an adjunctive therapy in experimental bacterial meningitis in the newborn piglet. Meningitis was induced by intracisternal injection of 10(8) colony-forming units of Escherichia coli in 100 microl of saline. Alpha-Phenyl-N-tert-butylnitrone 100 mg/kg was given as a bolus intravenous injection 30 min before induction of meningitis. Although it completely abolished the elevated CSF tumor necrosis factor-a level observed in the meningitis group, alpha-phenyl-N-tert-butylnitrone did not down-modulate parameters of inflammatory responses such as increased intracranial pressure, hypoglycorrhachia, elevated CSF lactate level, and CSF leukocytosis observed in this group. However, alpha-phenyl-N-tert-butylnitrone treatment mitigated alterations in brain cell membrane structure and function during meningitis, evidenced by amelioration of increased brain cell membrane lipid peroxidation products (conjugated dienes) and decreased Na+, K+-ATPase activity. Reduced mean arterial blood pressure, cerebral perfusion pressure, brain glucose concentration, and cerebral energy stores and marginally increased brain lactate level observed in the meningitis group were also ameliorated. These results suggest that although it failed to attenuate the inflammatory responses, alpha-phenyl-N-tert-butylnitrone was effective in ameliorating brain injury in neonatal bacterial meningitis.