title: Biphasic opening of the blood-brain barrier following transient focal ischemia: effects of hypothermia.
abstract: OBJECTIVE
  Tracer constants (Ki) for blood-to-brain diffusion of sucrose were measured in the rat to profile the time course of blood-brain barrier injury after temporary focal ischemia, and to determine the influence of post-ischemic hypothermia.
  
  
  METHODS
  Spontaneously hypertensive rats were subjected to transient (2 hours) clip occlusion of the right middle cerebral artery. Reperfusion times ranged from 1.5 min to 46 hours, and i.v. 3H-sucrose was circulated for 30 min prior to each time point (1 h, 4 h, 22 h, and 46 h; n = 5-7 per time point). Ki was calculated from the ratio of parenchymal tracer uptake and the time-integrated plasma concentration. Additional groups of rats (n = 7-8) were maintained either normothermic (37.5 degrees C) or hypothermic (32.5 degrees C or 28.5 degrees C) for the first 6 hours of reperfusion, and Ki was measured at 46 hours.
  
  
  RESULTS
  Rats injected after 1.5-2 min exhibited a 10-fold increase in Ki for cortical regions supplied by the right middle cerebral artery (p < 0.01). This barrier opening had closed within 1 to 4 hours post-reperfusion. By 22 hours, the blood-brain barrier had re-opened, with further opening 22 and 46 hours (p < 0.01), resulting in edema. Whole body hypothermia (28 degrees C-29 degrees C) during the first six hours of reperfusion prevented opening, reducing Ki by over 50% (p < 0.05).
  
  
  CONCLUSIONS
  Transient middle cerebral artery occlusion evokes a marked biphasic opening of the cortical blood-brain barrier, the second phase of which causes vasogenic edema. Hypothermic treatment reduced infarct volume and the late opening of the blood-brain barrier. This opening of the blood-brain barrier may enhance delivery of low permeability neuroprotective agents.
authors.affiliation: Alberta Stroke Program, Department of Clinical Neurosciences, University of Calgary, Canada.
authors.forename: Z G
authors.initials: ZG
authors.lastname: Huang
authors.forename: D
authors.initials: D
authors.lastname: Xue
authors.forename: E
authors.initials: E
authors.lastname: Preston
authors.forename: H
authors.initials: H
authors.lastname: Karbalai
authors.forename: A M
authors.initials: AM
authors.lastname: Buchan
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000502:physiology*; D001929:Brain Edema / Q000503:physiopathology / Q000628:therapy; D002540:Cerebral Cortex / Q000098:blood supply / Q000503:physiopathology; D002544:Cerebral Infarction / Q000503:physiopathology / Q000628:therapy; D003342:Corpus Striatum / Q000098:blood supply / Q000503:physiopathology; D006624:Hippocampus / Q000098:blood supply / Q000503:physiopathology; D007036:Hypothermia, Induced; D002546:Ischemic Attack, Transient / Q000503:physiopathology* / Q000628:therapy; D007700:Kinetics; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D013395:Sucrose / Q000493:pharmacokinetics*; D013525:Surgical Instruments; D014316:Tritium / Q000493:pharmacokinetics; D014867:Water / Q000378:metabolism
chemical_list: D014867:Water; D014316:Tritium; D013395:Sucrose