Expression of endothelial adhesion molecules after radiosurgery in an animal model of arteriovenous malformation.
BACKGROUND
Endothelial adhesion molecules may be important in the response of brain arteriovenous malformations (AVMs) to radiosurgery. In addition to a putative role in the occlusive process after radiosurgery, they may serve as potential targets for biological strategies to accelerate intravascular thrombosis.


OBJECTIVE
To determine the temporal expression of E-selectin and vascular cell adhesion molecule-1 in an animal model of AVMs.


METHODS
Forty-one Sprague-Dawley rats underwent surgical creation of a carotid-to-jugular anastomosis. Radiosurgery (25 Gy) was delivered to the model "nidus" after 6 weeks, and the tissue was harvested 1 to 84 days after radiosurgery. Control groups received sham irradiation. Immunofluorescence was used to study the expression of E-selectin and vascular cell adhesion molecule-1.


RESULTS
Endothelial E-selectin expression was limited to regions receiving radiosurgery. E-selectin expression reached maximal expression at 24 hours after radiosurgery and was sustained for another 24 hours before gradually reducing to baseline at 84 days post-radiosurgery (P < .01). Vascular cell adhesion molecule-1 expression remained at the baseline level for the first week; a 50% increase was observed at 21 days after radiosurgery, which was sustained for another 3 weeks before returning to the baseline at 84 days after radiosurgery (P < .05).


CONCLUSIONS
Radiosurgery stimulates early expression of E-selectin and delayed up-regulation of vascular cell adhesion molecule-1 on the endothelial surface of the AVM model nidus. Cell adhesion molecule expression may play an important role in the process leading to vascular obliteration after irradiation. These molecular alterations may be harnessed to promote thrombosis in the irradiated vasculature using a vascular targeting agent.
Storer
Kingsley P
KP
Prince of Wales Medical Research Institute, University of New South Wales, Sydney, Australia.
Tu
Jian
J
Stoodley
Marcus A
MA
Smee
Robert I
RI
D000818:Animals; D001165:Arteriovenous Malformations / Q000473:pathology* / Q000601:surgery*; D004195:Disease Models, Animal; D019040:E-Selectin / Q000378:metabolism; D004727:Endothelium / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D008297:Male; D016634:Radiosurgery / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
D019040:E-Selectin; D019010:Vascular Cell Adhesion Molecule-1