Mild hypothermia reduces ICAM-1 expression, neutrophil infiltration and microglia/monocyte accumulation following experimental stroke.
Mild hypothermia is an established neuroprotectant against cerebral ischemic injury. Studies have shown that inflammation potentiates cerebral ischemic injury, particularly in the setting of reperfusion. To further elucidate the mechanism by which mild hypothermia attenuates the inflammatory response, we assessed endothelial intercellular adhesion molecule-1 (ICAM-1) expression, neutrophil and monocyte infiltration, and microglial activation following 2 h of transient focal cerebral ischemia under normothermic and mildly hypothermic conditions. Ischemia was induced using the intraluminal suture method in Sprague-Dawley rats. Immunohistochemistry was used to detect endothelial ICAM-1, infiltrating neutrophils and monocytes, and microglia at 1, 3, and 7 days post-ischemia. Immunopositive cell and vessel densities were measured in the peri-infarct region. Mild hypothermia was associated with decreased neutrophils at 1 and 3 days post-ischemia, decreased ICAM-1-positive vessels at 1, 3, and 7 days, and decreased monocytes/activated microglia at 3 and 7 days, but not at 1 day. These data demonstrate that mild hypothermia significantly reduces endothelial adhesion molecule expression, acute (neutrophil) and subacute (monocyte) leukocyte infiltration, and microglial activation up to 7 days following insult in a rodent model of transient focal cerebral ischemia.
Wang
G J
GJ
Department of Neurosurgery, Stanford University, CA 94305, USA.
Deng
H Y
HY
Maier
C M
CM
Sun
G H
GH
Yenari
M A
MA
D000818:Animals; D004195:Disease Models, Animal; D007036:Hypothermia, Induced; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology / Q000628:therapy; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D002546:Ischemic Attack, Transient / Q000473:pathology / Q000628:therapy; D008297:Male; D017628:Microglia / Q000473:pathology*; D009000:Monocytes / Q000473:pathology; D009504:Neutrophils / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000473:pathology* / Q000628:therapy*
D018799:Intercellular Adhesion Molecule-1