Inducible nitric oxide synthase gene expression in the brain during systemic inflammation.

Abstract:

:Inducible nitric oxide synthase (iNOS) is a transcriptionally regulated enzyme that synthesizes nitric oxide from L-arginine that has a key role in the pathophysiology of systemic inflammation and sepsis. Transgenic animals with a null mutation for the iNOS gene are resistant to hypotension and death caused by Escherichia coli lipopolysaccharide (LPS). The regulation of peripheral iNOS has been well studied in sepsis, but little is known about iNOS regulation in the brain during systemic inflammation or sepsis. We know that at baseline there is no detectable iNOS gene expression in the brain, but a detailed neuroanatomical study reveals that early in the course of systemic inflammation there is a profound induction of iNOS messenger RNA in vascular, glial and neuronal structures of the rat brain, accompanied by the production of nitric oxide (NO) metabolites in brain parenchyma and cerebrospinal fluid (CSF). We propose that the spillover of nitrite into the CSF has the potential to be a diagnostic marker for systemic inflammation and sepsis. Pharmacological interventions aimed at regulating iNOS function in the brain might represent a new treatment strategy in sepsis. Brain iNOS may be relevant to the pathophysiology, diagnosis and treatment of systemic inflammation and sepsis.

journal_name

Nat Med

journal_title

Nature medicine

authors

Wong ML,Rettori V,al-Shekhlee A,Bongiorno PB,Canteros G,McCann SM,Gold PW,Licinio J

doi

10.1038/nm0596-581

subject

Has Abstract

pub_date

1996-05-01 00:00:00

pages

581-4

issue

5

eissn

1078-8956

issn

1546-170X

journal_volume

2

pub_type

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