Mild hypothermia inhibits nuclear factor-κB translocation in experimental stroke

Hyung Soo Han, Murat Karabiyikoglu, Stephen Kelly, Raymond A. Sobel, Midori A. Yenari

Research output: Contribution to journalArticlepeer-review

125 Scopus citations

Abstract

Nuclear factor-κB (NFκB) is a transcription factor that is activated after cerebral ischemia. NFκB activation leads to the expression of many inflammatory genes involved in the pathogenesis of stroke. The authors previously showed that mild hypothermia is protective even when cooling begins 2 h after stroke onset. In the present study, they examined the influence of hypothermia on NFκB activation. Rats underwent 2 h of transient middle cerebral artery occlusion. Brains were cooled to 33°C immediately after or 2 h after occlusion, and maintained for 2 h. After normothermic ischemia (brain temperature at 38°C), NFκB cytoplasmic expression, nuclear translocation, and binding activity were observed as early as 2 h in the ischemic hemisphere and persisted at 24 h. Hypothermia decreased NFκB translocation and binding activity but did not alter overall expression. Hypothermia also affected the levels of NFκB regulatory proteins by suppressing phosphorylation of NFκB's inhibitory protein (IκB-α) and IκB kinase (IKK-γ) and decreasing IKK activity, but did not alter overall IKK levels. Hypothermia suppressed the expression of two NFκB target genes: inducible nitric oxide synthase and TNF-α. These data suggest that the protective effect of hypothermia on cerebral injury is, in part, related to NFκB inhibition due to decreased activity of IKK.

Original languageEnglish
Pages (from-to)589-598
Number of pages10
JournalJournal of Cerebral Blood Flow and Metabolism
Volume23
Issue number5
DOIs
StatePublished - 1 May 2003

Keywords

  • Hypothermia
  • Inflammation
  • Nuclear factorκB
  • Stroke

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