Effect of transient focal ischemia on blood-brain barrier permeability in the rat: correlation to cell injury.
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.
Albayrak
S
S
Laboratory for Experimental Brain Research, Wallenberg Neuroscience Center, University of Lund, University Hospital, Sweden.
Zhao
Q
Q
Siesjö
B K
BK
Smith
M L
ML
D000418:Albumins / Q000378:metabolism; D000621:Aminoisobutyric Acids / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure; D001812:Blood-Brain Barrier / Q000502:physiology*; D001831:Body Temperature; D002199:Capillary Permeability / Q000502:physiology*; D002245:Carbon Dioxide / Q000097:blood; D002536:Cerebral Arteries / Q000503:physiopathology; D002540:Cerebral Cortex / Q000187:drug effects / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D007150:Immunohistochemistry; D002546:Ischemic Attack, Transient / Q000503:physiopathology*; D008297:Male; D009474:Neurons / Q000166:cytology / Q000473:pathology / Q000502:physiology; D010100:Oxygen / Q000097:blood; D011699:Putamen / Q000187:drug effects / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D000418:Albumins; D000621:Aminoisobutyric Acids; D002245:Carbon Dioxide; D010100:Oxygen