Mild Hypothermia Attenuates Intercellular Adhesion Molecule-1 Induction via Activation of Extracellular Signal-Regulated Kinase-12 in a Focal Cerebral Ischemia Model

Abstract EN

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.