Mild hypothermia attenuates intercellular adhesion molecule-1 induction via activation of extracellular signal-regulated kinase-1/2 in a focal cerebral ischemia model

Hyung Soo Han, Jung Sook Choi, Jaechan Park, Kyoungho Suk, Cheil Moon, Yong Ki Park

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Intercellular adhesion molecule-1 (ICAM-1) in cerebral vascular endothelium induced by ischemic insult triggers leukocyte infiltration and inflammatory reaction. We investigated the mechanism of hypothermic suppression of ICAM-1 in a model of focal cerebral ischemia. Rats underwent 2 hours of middle cerebral artery occlusion and were kept at 37()C or 33()C during occlusion and rewarmed to normal temperature immediately after reperfusion. Under hypothermic condition, robust activation of extracellular signal-regulated kinase-1/2 (ERK1/2) was observed in vascular endothelium of ischemic brain. Hypothermic suppression of ICAM-1 was reversed by ERK1/2 inhibition. Phosphorylation of signal transducer and activator of transcription 3 (STAT3) in ischemic vessel was attenuated by hypothermia. STAT3 inhibitor suppressed ICAM-1 production induced by stroke. ERK1/2 inhibition enhanced phosphorylation and DNA binding activity of STAT3 in hypothermic condition. In this study, we demonstrated that hypothermic suppression of ICAM-1 induction is mediated by enhanced ERK1/2 activation and subsequent attenuation of STAT3 action.

Original languageEnglish (US)
Title of host publicationStroke Research and Treatment
DOIs
StatePublished - 2011
Externally publishedYes

ASJC Scopus subject areas

  • Clinical Neurology

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