REACTIVE OXYGEN INTERMEDIATES CONTRIBUTE TO NECROTIC AND APOPTOTIC NEURONAL INJURY IN AN INFANT RAT MODEL OF BACTERIAL-MENINGITIS DUE TO GROUP-B STREPTOCOCCI

Reactive oxygen intermediates (ROI) contribute to neuronal injury in c erebral ischemia and trauma. In this study we explored the role of ROI in bacterial meningitis. Meningitis caused by group B streptococci in infant rats led to two distinct forms of neuronal injury, areas of ne crosis in the cortex and neuronal loss in the dentate gyrus of the hip pocampus, the latter showing evidence for apoptosis. Staining of brain sections with diaminobenzidine after perfusion with manganese buffer and measurement of lipid peroxidation products in brain homogenates bo th provided evidence that meningitis led to the generation of ROI. Tre atment with the radical scavenger alpha-phenyl-tert-butyl nitrone (PEN ) (100 mg/kg q8h i.p.) beginning at the time of infection completely a bolished ROI detection and the increase in lipidperoxidation. Cerebral cortical perfusion was reduced in animals with meningitis to 37.5 +/- 21.0% of uninfected controls (P < 0.05), and PEN restored cortical pe rfusion to 72.0 +/- 8.1% of controls (P < 0.05 vs meningitis). PEN als o completely prevented neuronal injury in the cortex and hippocampus, when started at the time of infection (P < 0.02), and significantly re duced both forms of injury, when started 18 h after infection together with antibiotics (P < 0.004 for cortex and P < 0.001 for hippocampus) . These data indicate that the generation of ROI is a major contributo r to cerebral ischemia and necrotic and apoptotic neuronal injury in t his model of neonatal meningitis.