Effect of transient focal ischemia on blood-brain barrier permeability in the rat: correlation to cell injury

Acta Neuropathol. 1997 Aug;94(2):158-63. doi: 10.1007/s004010050688.


Prolonged ischemia is known to damage the blood-brain barrier, causing an increase in vascular permeability to proteins. We studied the time course of extravasation of endogenous albumin in rats after 1 and 2 h of middle cerebral artery (MCA) occlusion followed by 6, 12, and 24 h of recirculation. In a separate group of rats that had undergone 1 h of MCA occlusion and 6 h of recirculation, influx of [14C]aminoisobutyric acid (AIB) from blood to brain was also measured. After 1 h of occlusion followed by 6 h of recirculation, neuronal damage was evident in caudoputamen, but there were no signs of blood-brain barrier leakage to either AIB or albumin. At 12 h, the caudoputamen contained extravasated albumin, and at 24 h extravasation was extended to the somatosensory cortex. Animals subjected to 2 h of MCA occlusion showed albumin extravasation in caudoputamen already at 6 h of recirculation, and at 12 and 24 h albumin was abundant in the major part of the right hemisphere. This study suggests that damage to neurons precedes leakage of the blood-brain barrier. Even a relatively short period of ischemia such as 1 h will result in markedly increased vascular permeability. However, a longer transient ischemic insult disrupts the blood-brain barrier earlier than a shorter one.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Albumins / metabolism
  • Aminoisobutyric Acids / pharmacology
  • Animals
  • Blood Pressure
  • Blood-Brain Barrier / physiology*
  • Body Temperature
  • Capillary Permeability / physiology*
  • Carbon Dioxide / blood
  • Cerebral Arteries / physiopathology
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / physiopathology
  • Cerebrovascular Circulation / drug effects
  • Cerebrovascular Circulation / physiology
  • Hydrogen-Ion Concentration
  • Immunohistochemistry
  • Ischemic Attack, Transient / physiopathology*
  • Male
  • Neurons / cytology
  • Neurons / pathology
  • Neurons / physiology
  • Oxygen / blood
  • Putamen / drug effects
  • Putamen / physiopathology
  • Rats
  • Rats, Wistar
  • Time Factors


  • Albumins
  • Aminoisobutyric Acids
  • Carbon Dioxide
  • Oxygen