Hypothermia suppresses inflammation via ERK signaling pathway in stimulated microglial cells

J Neuroimmunol. 2007 Sep;189(1-2):7-16. doi: 10.1016/j.jneuroim.2007.06.010. Epub 2007 Jul 24.

Abstract

Hypothermic perfusion is a standard method for neuroprotection during cardiac surgery in children. However, the cellular responses underlying these mechanisms have not been clearly elucidated. In the present study we demonstrated that the inflammatory response of stimulated microglial cells is significantly reduced after moderate hypothermia. Continuous hypothermia caused a diminished NO release. Moderate hypothermia and rewarming caused a downregulation of phosphorylated MEK, ERK and iNOS-expression, diminished cytokine release and reduced CD-11a and ICAM-1 expression. Thus, neuroprotection offered by hypothermia could be attributed to reduced cytotoxic products released from stimulated microglial cells mediated by the MEK/ERK signal transduction pathway.

MeSH terms

  • Animals
  • Animals, Newborn
  • Cell Count
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Cells, Cultured
  • Cold Temperature
  • Enzyme-Linked Immunosorbent Assay / methods
  • Extracellular Signal-Regulated MAP Kinases / physiology*
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology*
  • Hypothermia*
  • Interleukin-6 / metabolism
  • Mice
  • Microglia / drug effects
  • Microglia / physiology*
  • Nitric Oxide Synthase Type II / metabolism
  • Polysaccharides / adverse effects
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*
  • Tetrazolium Salts
  • Thiazoles
  • Time Factors
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Interleukin-6
  • Polysaccharides
  • Tetrazolium Salts
  • Thiazoles
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide Synthase Type II
  • Extracellular Signal-Regulated MAP Kinases
  • thiazolyl blue