title: Inducible nitric oxide synthase and the effect of aminoguanidine in experimental neonatal meningitis.
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.
authors.affiliation: Infectious Diseases Laboratory, San Francisco General Hospital, University of California, USA.
authors.forename: S L
authors.initials: SL
authors.lastname: Leib
authors.forename: Y S
authors.initials: YS
authors.lastname: Kim
authors.forename: S M
authors.initials: SM
authors.lastname: Black
authors.forename: J H
authors.initials: JH
authors.lastname: Tureen
authors.forename: M G
authors.initials: MG
authors.lastname: Täuber
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002545:Brain Ischemia / Q000378:metabolism; D002490:Central Nervous System / Q000201:enzymology / Q000473:pathology; D006146:Guanidines / Q000494:pharmacology*; D016920:Meningitis, Bacterial / Q000201:enzymology* / Q000473:pathology; D009474:Neurons / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D017207:Rats, Sprague-Dawley; D013290:Streptococcal Infections / Q000201:enzymology* / Q000473:pathology; D013292:Streptococcus agalactiae
chemical_list: D006146:Guanidines; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; C004479:pimagedine