Influence of hypothermia on post-ischemic inflammation:: Role of nuclear factor kappa B (NFκB)

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-kappa B (NF kappa B) is a transcription factor that is activated after cerebral ischemia. NF kappa B activation leads to the expression of many inflammatory genes involved in the pathogenesis of stroke. Our laboratory has shown that hypothermia decreases NF kappa B translocation and binding activity, by affecting NF kappa B regulatory proteins. Mild hypothermia appears to suppress phosphorylation of NF kappa B's inhibitory protein (I kappa B-alpha) by decreasing expression and activity of I kappa B kinase-gamma (IKK). As a consequence, hypothermia suppressed gene expression of two NF kappa B 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 NF kappa B inhibition due to decreased activity of IKK. (c) 2006 Elsevier Ltd. All rights reserved.