Inducible Nitric Oxide Synthase and the Effect of Aminoguanidine in Experimental Neonatal Meningitis

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Abstract

This study explored the role of inducible nitric oxide (NO) synthase (iNOS) in an infant rat model of group B streptococcal meningitis. Brain iNOS activity increased during meningitis (P < .001), and iNOS was detected by immunocytochemistry in the walls of meningeal vessels and cells of the cerebrospinal fluid (CSF) inflammation. Animals treated with iNOS inhibitor aminoguanidine (AG; 130 mg/kg every 8 h) had reduced NO production (P < .05), higher CSF bacterial titers (P < .05), and increased incidence of seizures (P < .01) compared with untreated infected animals. AG also increased areas of severe hypoperfusion in the cortex (31% ± 14% in controls vs. 56% ± 16% in AG; P < .01) and the extent of cortical neuronal injury, both when administered at the time of infection (P < .05) and in established meningitis (P < .02). Thus, NO produced by iNOS may be beneficial in this model of experimental meningitis by reducing cerebral ischemia.

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