title: Mild hypothermia inhibits inflammation after experimental stroke and brain inflammation.
abstract: OBJECTIVE
  We previously showed that mild hypothermia protects against experimental stroke, even when cooling was delayed by 2 hours. Protection may be due in part to inhibiting inflammation. To clarify, we examined leukocyte infiltration, microglial activation, and adhesion molecule expression in models of stroke and pure brain inflammation.
  
  
  METHODS
  Rats underwent 2-hour middle cerebral artery occlusion (MCAO; n=36) or intravenous injection with 5 mg/kg lipopolysaccharide (LPS; n=22). Temperature was lowered to 33 degrees C for 2 hours or kept at 37 degrees C. In MCAO, cooling was applied intraischemically or on reperfusion (delayed). In the LPS model, cooling began after injection. One and 3 days later, brains were assessed for neutrophils, monocytes/microglia, major histocompatibility complex class II antigen, and intercellular adhesion molecule-1 (ICAM-1).
  
  
  RESULTS
  One day after MCAO, both intraischemic and delayed hypothermia decreased ICAM-1 (51% and 60%, respectively, versus normothermia; P<0.001), monocytes (63% and 57%; P<0.01), and microglia (55% and 53%; P<0.001). Similar decreases were seen at 3 days for ICAM-1 (91% and 93%; P<0.001), monocytes (62% and 54%; P<0.01), and microglia (55% and 53%; P<0.001). In the LPS model, ED-1-positive cells were not observed in the brain, but hypothermia decreased ICAM-1 (26%; P<0.05), OX6 (56%; P<0.01), and microglia (47%; P<0.01) at 1 day.
  
  
  CONCLUSIONS
  Mild hypothermia decreases inflammatory responses in both brain inflammation and stroke, implicating a direct anti-inflammatory effect of cooling. This suggests that hypothermia can attenuate factors contributing to delayed ischemic injury.
authors.affiliation: Departments of Neurosurgery, Stanford University, Stanford, Calif, USA.
authors.forename: Holly
authors.initials: H
authors.lastname: Deng
authors.forename: Hyung Soo
authors.initials: HS
authors.lastname: Han
authors.forename: Danye
authors.initials: D
authors.lastname: Cheng
authors.forename: Guo Hua
authors.initials: GH
authors.lastname: Sun
authors.forename: Midori A
authors.initials: MA
authors.lastname: Yenari
mesh_terms: D000818:Animals; D001831:Body Temperature; D001921:Brain / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D015816:Cell Adhesion Molecules, Neuronal / Q000096:biosynthesis; D004195:Disease Models, Animal; D018450:Disease Progression; D004660:Encephalitis / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D007036:Hypothermia, Induced / Q000379:methods*; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000473:pathology / Q000628:therapy; D018799:Intercellular Adhesion Molecule-1; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D017628:Microglia / Q000473:pathology; D009000:Monocytes / Q000473:pathology; D009504:Neutrophils / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000150:complications / Q000473:pathology / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D008070:Lipopolysaccharides; D018799:Intercellular Adhesion Molecule-1