Early blood-brain barrier changes in the rat following transient complete cerebral ischemia induced by cardiac arrest

Brain Res. 1994 Jan 7;633(1-2):41-52. doi: 10.1016/0006-8993(94)91520-2.


This study examined regional patterns of increased vascular permeability following transient global cerebral ischemia. Rats underwent 3.5, 5 or 10 min of cardiac vessel bundle occlusion, i.e. cardiac arrest. The animals were killed at 2, 3, 5 and 15 min, or 1, 3, 6 and 24 h after global cerebral ischemia. Thirty minutes before the end of each blood recirculation period, the electron dense protein tracer--horseradish peroxidase (HRP) was intravenously injected and rats were perfusion-fixed for light and electron microscopic analysis. Control rats showed no HRP leakage. Post-ischemic rats demonstrated random blood-brain barrier (BBB) alterations. Permeability alterations were spotty and widespread in cortical, thalamic, basal ganglia, hippocampal, brain stem regions, cerebellum and white matter. Peroxidase extravasation frequently involved arterioles, veins and venules surrounded by perivascular spaces. Routes of increased HRP permeability included endothelial cell (EC) vesiculo-canalicular profiles and diffuse leakage through damaged ECs. Barrier damage determined by HRP permeability revealed a biphasic nature. The first stage appeared immediately after ischemia at the 2nd min and involved the 1st post-insult hour. There was no HRP leakage in rats sacrificed 3 h after insult. BBB opening appeared again 6 h after ischemia and remained open 24 h after cardiac arrest. The openings of BBB did not increase in frequency with longer periods of ischemia and recirculation. These results demonstrate that cardiac arrest produces a spotty BBB disturbances at vessel bifurcations and suggest that BBB changes associated with cardiac arrest may be multifactorial in time course and location.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood-Brain Barrier / physiology*
  • Brain / pathology
  • Female
  • Heart Arrest / complications
  • Heart Arrest / pathology*
  • Histocytochemistry
  • Horseradish Peroxidase
  • Ischemic Attack, Transient / etiology
  • Ischemic Attack, Transient / pathology*
  • Male
  • Proteins / metabolism
  • Rats
  • Rats, Wistar
  • Time Factors


  • Proteins
  • Horseradish Peroxidase