Cerebral blood flow restoration and reperfusion injury after ultraviolet laser-facilitated middle cerebral artery recanalization in rat thrombotic stroke.
OBJECTIVE
A reversible model of focal thrombotic stroke was developed in the rat and examined for histological evidence of reperfusion injury after clinically relevant times of recanalization.


METHODS
The distal middle cerebral artery of 28 male Sprague-Dawley rats was occluded by 562-nm laser-driven photothrombosis for 0.5, 2, and 3 hours or permanently (each n=7) and was recanalized by 355-nm UV laser irradiation. Occlusive material was examined by transmission electron microscopy. Cortical cerebral blood flow was monitored by laser-Doppler flowmetry. Brain infarcts were examined histologically at 3 days.


RESULTS
After occlusion, cortical cerebral blood flow was reduced to 33+/-4% of baseline for all groups and was restored to 82+/-9%, 75+/-3%, and 93+/-7% of baseline for the 0.5-, 2-, and 3-hour groups, respectively, following recanalization after 29+/-8, 38+/-20, and 70+/-33 minutes of UV laser irradiation. The thrombotic occlusion contained compactly aggregated platelets but no fibrin, with length (1.2 to 1.8 mm) proportional to the ischemic period. During recanalization, microchannels containing erythrocytes and scattered leukocytes and bordered by intact disaggregated platelets infiltrated the thrombus. Infarct volumes (mm3) at 3 days were 12+/-3 for the permanent case and 8+/-4, 24+/-3, and 30+/-9 for the 0.5-, 2-, and 3-hour cases, respectively, thus demonstrating reperfusion injury histologically in the latter 2 groups. No hemorrhage was seen.


CONCLUSIONS
UV laser-facilitated dissolution of a conventionally refractory platelet thrombus provides a novel and effective method for restoring blood flow without hemorrhagic complications during thrombotic stroke. This was the first observation of histologically confirmed reperfusion injury in such a model.
Watson
Brant D
BD
Cerebral Vascular Disease Research Center, Department of Neurology, University of Miami School of Medicine, Fla 33101, USA. brant@stroke.med.miami.edu
Prado
Ricardo
R
Veloso
Alexander
A
Brunschwig
J-P
JP
Dietrich
W Dalton
WD
D016342:Angioplasty, Laser / Q000009:adverse effects; D000818:Animals; D001783:Blood Flow Velocity; D002560:Cerebrovascular Circulation; D004195:Disease Models, Animal; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000503:physiopathology / Q000628:therapy*; D017075:Laser Coagulation; D017078:Laser-Doppler Flowmetry; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000209:etiology; D020521:Stroke / Q000150:complications / Q000503:physiopathology / Q000628:therapy*; D013997:Time Factors