Hypothermia suppresses inflammation via ERK signaling pathway in stimulated microglial cells.
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.
Schmitt
Katharina Rose Luise
KR
Department of Congenital Heart Disease / Pediatric Cardiology, Deutsches Herzzentrum Berlin, Augustenburger Platz 1, 13353 Berlin, Germany. katharina.schmitt@charite.de
Diestel
Antje
A
Lehnardt
Seija
S
Schwartlander
Ruth
R
Lange
Peter E
PE
Berger
Felix
F
Ullrich
Oliver
O
Abdul-Khaliq
Hashim
H
D000818:Animals; D000831:Animals, Newborn; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003080:Cold Temperature; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D007035:Hypothermia; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D011134:Polysaccharides / Q000009:adverse effects; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013778:Tetrazolium Salts; D013844:Thiazoles; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015850:Interleukin-6; D011134:Polysaccharides; D013778:Tetrazolium Salts; D013844:Thiazoles; D014409:Tumor Necrosis Factor-alpha; D052247:Nitric Oxide Synthase Type II; D048049:Extracellular Signal-Regulated MAP Kinases; C022616:thiazolyl blue