Spin trapping agent, phenyl N-tert-butylnitrone, reduces nitric oxide production in the rat brain during experimental meningitis.
Phenyl N-tert-butylnitrone (PBN) is a spin trapping agent previously shown to exert a neuroprotective effect in infant rat brain during bacterial meningitis. In the present study, we investigated the effect of systemic PBN administration on nitric oxide (NO) production in a rat model of experimental meningitis induced by lipopolysaccharide (LPS). We assessed the NO concentration in rat brain tissues with an electron paramagnetic resonance (EPR) NO trapping technique. In this model, rats receiving intracisternal LPS administration showed symptoms of meningitis and cerebrospinal fluid (CSF) pleocytosis. The time course study indicated that the concentration of NO in the brain reached the maximum level 8.5 h after injection of LPS, and returned to the control level 24 h after the injection. When various doses of PBN (125-400 mg/kg) were injected intraperitoneally 30 min prior to LPS, NO production in the brain was reduced with increasing PBN dose (250 mg/kg suppressed 80% at 8.5 h after LPS injection), and white blood cells (WBC) in CSF were significantly decreased. We concluded that reduction of NO generation during bacterial meningitis contributes to the neuroprotective effect of PBN in addition to its possible direct scavenging of reactive oxygen intermediate (ROI).
Endoh
H
H
Institute for Life Support Technology, Yamagata Public Corporation for the Development of Industry, 2-2-1 Matsuei, Yamagata 990-2473, Japan.
Kato
N
N
Fujii
S
S
Suzuki
Y
Y
Sato
S
S
Kayama
T
T
Kotake
Y
Y
Yoshimura
T
T
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D003497:Cyclic N-Oxides; D004578:Electron Spin Resonance Spectroscopy; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D008070:Lipopolysaccharides / Q000633:toxicity; D016920:Meningitis, Bacterial / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D009589:Nitrogen Oxides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013113:Spin Labels; D019097:Spin Trapping; D019323:omega-N-Methylarginine / Q000494:pharmacology
D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers; D008070:Lipopolysaccharides; D018696:Neuroprotective Agents; D009589:Nitrogen Oxides; D013113:Spin Labels; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; C029217:phenyl-N-tert-butylnitrone; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat