Biphasic opening of the blood-brain barrier following transient focal ischemia: effects of hypothermia

Can J Neurol Sci. 1999 Nov;26(4):298-304. doi: 10.1017/s0317167100000421.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood-Brain Barrier / physiology*
  • Brain Edema / physiopathology
  • Brain Edema / therapy
  • Cerebral Cortex / blood supply
  • Cerebral Cortex / physiopathology
  • Cerebral Infarction / physiopathology
  • Cerebral Infarction / therapy
  • Corpus Striatum / blood supply
  • Corpus Striatum / physiopathology
  • Hippocampus / blood supply
  • Hippocampus / physiopathology
  • Hypothermia, Induced*
  • Ischemic Attack, Transient / physiopathology*
  • Ischemic Attack, Transient / therapy
  • Kinetics
  • Male
  • Rats
  • Rats, Inbred SHR
  • Sucrose / pharmacokinetics*
  • Surgical Instruments
  • Tritium / pharmacokinetics
  • Water / metabolism


  • Water
  • Tritium
  • Sucrose