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Influence of hypothermia on post-ischemic inflammation: role of nuclear factor kappa B (NFkappaB).
- Source :
-
Neurochemistry international [Neurochem Int] 2006 Jul; Vol. 49 (2), pp. 164-9. Date of Electronic Publication: 2006 Jun 05. - Publication Year :
- 2006
-
Abstract
- Mild hypothermia is one of the most robust neuroprotectant studied in the laboratory to date. The reasons for this protective effect are likely multifactorial, but work from our laboratory and others have shown that this protection is associated with remarkable suppression of the inflammatory response that accompanies brain ischemia. Consistently, laboratories have shown that small decreases in brain temperature to 30-34 degrees C result in reduced inflammatory cell infiltrate, less microglial activation, and reduction of a variety of inflammatory mediators such as nitric oxide, inflammatory cytokines and superoxide. Nuclear factor-kappaB (NFkappaB) is a transcription factor that is activated after cerebral ischemia. NFkappaB activation leads to the expression of many inflammatory genes involved in the pathogenesis of stroke. Our laboratory has shown that hypothermia decreases NFkappaB translocation and binding activity, by affecting NFkappaB regulatory proteins. Mild hypothermia appears to suppress phosphorylation of NFkappaB's inhibitory protein (IkappaB-alpha) by decreasing expression and activity of IkappaB kinase-gamma (IKK). As a consequence, hypothermia suppressed gene expression of two NFkappaB target genes, inducible nitric oxide synthase and TNF-alpha. These data suggest that the protective effect of hypothermia on cerebral injury is, in part, related to NFkappaB inhibition due to decreased activity of IKK.
- Subjects :
- Animals
Body Temperature physiology
Brain metabolism
Brain physiopathology
Brain Ischemia metabolism
Encephalitis physiopathology
Gene Expression Regulation genetics
Gene Expression Regulation immunology
Humans
I-kappa B Proteins metabolism
Inflammation Mediators metabolism
Brain Ischemia physiopathology
Cytoprotection physiology
Encephalitis prevention & control
Encephalitis therapy
Hypothermia, Induced
NF-kappa B metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0197-0186
- Volume :
- 49
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Neurochemistry international
- Publication Type :
- Academic Journal
- Accession number :
- 16750872
- Full Text :
- https://doi.org/10.1016/j.neuint.2006.03.016