Reperfusion-induced injury to the blood-brain barrier after middle cerebral artery occlusion in rats.
OBJECTIVE
The integrity of the blood-brain barrier may play an important pathophysiological role during postischemic reperfusion. To determine the factors that lead to exacerbation of brain injury by reperfusion, we investigated changes in cerebral blood flow, blood-brain barrier permeability, edema formation, and infarction in permanent or temporary middle cerebral artery occlusion in rats and studied the relation between local cerebral blood flow and blood-brain barrier disruption.


METHODS
Middle cerebral artery occlusion was performed with the rat suture model, allowing either permanent (6 hours) or temporary occlusion (3 hours of occlusion and 3 hours of reperfusion). We measured brain water, ion contents, and infarct volumes and determined cerebral blood flow using laser Doppler flowmetry and blood-brain barrier permeability with [3H] alpha-aminoisobutyric acid.


RESULTS
During occlusion, cerebral blood flow was reduced to 7% to 15% (permanent) and 10% to 17% (temporary) of the baseline. During 3 hours of reperfusion, it returned to 47% to 80% (lateral cortex) and 78% to 98% (medial cortex) of the baseline. Compared with the contralateral hemisphere, the water content in the ischemic area increased in both permanent and temporary groups (P < .05, P < .01). Both infarct volume and blood-brain barrier disruption were greater in the reperfusion group compared with the permanent occlusion group (P < .05). Blood-brain barrier disruption correlated with cerebral blood flow during reperfusion (P < .05).


CONCLUSIONS
These findings demonstrate that brain infarct and blood-brain barrier disruption are exacerbated after reperfusion in this model of focal ischemia. Blood-brain barrier disruption may relate to the degree of cerebral blood flow recovery. Thus, although early reperfusion in focal ischemia may preserve penumbra tissue, late reperfusion may increase the tissue injury.
Yang
G Y
GY
Department of Surgery (Neurosurgery), University of Michigan Medical Center, Ann Arbor 48109-0532.
Betz
A L
AL
D000818:Animals; D001794:Blood Pressure; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism / Q000473:pathology; D001929:Brain Edema / Q000209:etiology* / Q000378:metabolism; D002536:Cerebral Arteries / Q000503:physiopathology; D002544:Cerebral Infarction / Q000209:etiology*; D002560:Cerebrovascular Circulation; D002712:Chlorides / Q000378:metabolism; D008297:Male; D011188:Potassium / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000503:physiopathology*; D012964:Sodium / Q000378:metabolism
D002712:Chlorides; D012964:Sodium; D011188:Potassium