Inflammation and NFkappaB activation is decreased by hypothermia following global cerebral ischemia.
We previously showed that hypothermia attenuates inflammation in focal cerebral ischemia (FCI) by suppressing activating kinases of nuclear factor-kappa B (NFkappaB). Here we characterize the inflammatory response in global cerebral ischemia (GCI), and the influence of mild hypothermia. Rodents were subjected to GCI by bilateral carotid artery occlusion. The inflammatory response was accompanied by microglial activation, but not neutrophil infiltration, or blood brain barrier disruption. Mild hypothermia reduced CA1 damage, decreased microglial activation and decreased nuclear NFkappaB translocation and activation. Similar anti-inflammatory effects of hypothermia were observed in a model of pure brain inflammation that does not cause brain cell death. Primary microglial cultures subjected to oxygen glucose deprivation (OGD) or stimulated with LPS under hypothermic conditions also experienced less activation and less NFkappaB translocation. However, NFkappaB regulatory proteins were not affected by hypothermia. The inflammatory response following GCI and hypothermia's anti-inflammatory mechanism is different from that observed in FCI.
Webster
Carla M
CM
Department of Neurology, University of California, San Francisco and the San Francisco Veterans Affairs Medical Center, 4150 Clement Street, San Francisco, CA 94121, USA.
Kelly
Stephen
S
Koike
Maya A
MA
Chock
Valerie Y
VY
Giffard
Rona G
RG
Yenari
Midori A
MA
D000818:Animals; D001812:Blood-Brain Barrier / Q000502:physiology; D002545:Brain Ischemia / Q000276:immunology* / Q000628:therapy*; D002339:Carotid Arteries; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D005947:Glucose / Q000172:deficiency; D006624:Hippocampus / Q000503:physiopathology; D007036:Hypothermia, Induced; D007249:Inflammation / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000502:physiology; D016328:NF-kappa B / Q000378:metabolism*; D009504:Neutrophils / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
D016328:NF-kappa B; D005947:Glucose