Korean J Physiol Pharmacol.  2004 Aug;8(4):187-194.

Effect of Mild Hypothermia on the Mitogen Activated Protein Kinases in Experimental Stroke

• Han HS

Abstract

Middle cerebral artery occlusion (MCAO) results in cell death by activation of complex signal pathways for cell death and survival. Hypothermia is a robust neuroprotectant, and its effect has often been attributed to various mechanisms, but it is not yet clear. Upstream from the cell death promoters and executioners are several enzymes that may activate several transcription factors involved in cell death and survival. In this study, we immunohistochemically examined the phosphorylation of mitogen- activated protein kinase, extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 kinase during early period of the ischemic injury, following 2 hours (h) of transient MCAO. Increased phosphorylation of ERK and p38 was observed in the vessels at 3 h, neuron-like cells at 6 and 12 h and glia-like cells at 12 h. Activation of JNK was not remarkable, and a few cells showed active JNK following ischemia. Phosphorylation of Elk-1, a transcription factor, was reduced by ischemic insult. Hypothermia attenuated the activation of ERK, p38 and JNK, and inhibited reduction of Elk-1. These data suggest that signals via different MAPK family members converge on the cell damage process and hypothermia protects the brain by interfering with these pathways.

Keyword

Hypothermia; MAPK; Focal cerebral ischemia

MeSH Terms

Brain
Cell Death
Humans
Hypothermia*
Infarction, Middle Cerebral Artery
Ischemia
JNK Mitogen-Activated Protein Kinases
Mitogen-Activated Protein Kinases*
Phosphorylation
Phosphotransferases
Protein Kinases
Signal Transduction
Stroke*
Transcription Factors
JNK Mitogen-Activated Protein Kinases
Mitogen-Activated Protein Kinases
Phosphotransferases
Protein Kinases
Transcription Factors