Inducible nitric oxide synthase and the effect of aminoguanidine in experimental neonatal meningitis.
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.
Leib
S L
SL
Infectious Diseases Laboratory, San Francisco General Hospital, University of California, USA.
Kim
Y S
YS
Black
S M
SM
Tureen
J H
JH
Täuber
M G
MG
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
D006146:Guanidines; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; C004479:pimagedine