Stereotactic radiosurgery of the rete mirabile in swine: a longitudinal study of histopathological changes.
OBJECTIVE
Stereotactic radiosurgery is an established, effective treatment for brain arteriovenous malformations. The mechanisms of vessel occlusion in arteriovenous malformations has not been extensively evaluated. To better understand these mechanisms, we report histopathological changes in the swine rete mirabile after stereotactic radiosurgery.


METHODS
Thirty-five swine were used, 15 as nonradiated controls and 20 as radiated. Two in the control group and five in the radiated group were sacrificed before the study endpoint. Tissue was obtained from 13 nonradiated (4 at 3 mo, 5 at 6 mo, 4 at 9 mo) and 15 radiated swine (2 at 3 mo, 3 at 6 mo, 10 at 9 mo) for histological, immunohistochemical, and morphometric analysis.


RESULTS
Radiated vessels showed increasing intimal hyperplasia over the follow-up period. Histometrical analysis confirmed this with evidence of progressive luminal narrowing over the follow-up period. Immunohistochemical analysis showed intimal cells to be proliferating smooth muscle cells with surrounding extracellular collagen Type IV. Adventitial fibrosis composed of collagen Type IV was also seen with smooth muscle cells interspersed within the collagen matrix. The nonradiated animals showed no intimal hyperplasia or change in the appearance or size of the vessels over the same follow-up period. Adventitial fibrosis was minimal in the nonradiated animals.


CONCLUSIONS
The vessels show an intimal response to radiation with progressive occlusion caused by migrating, proliferating smooth muscle cells, a likely source of the extracellular collagen in the intima. Cytokine mediated pathways likely produce these morphological changes. Future studies will be directed toward elucidating these underlying molecular mechanisms.
Jahan
Reza
R
Division of Interventional Neuroradiology, Department of Radiological Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA. rjahan@mednet.ucla.edu
Solberg
Timothy D
TD
Lee
Daniel
D
Medin
Paul
P
Tateshima
Satoshi
S
Sayre
James
J
De Salles
Antonio
A
Vinters
Harry V
HV
Vinuela
Fernando
F
D000818:Animals; D001921:Brain / Q000098:blood supply* / Q000473:pathology*; D002343:Carotid Artery, Internal / Q000473:pathology; D005260:Female; D008137:Longitudinal Studies; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000473:pathology*; D016634:Radiosurgery / Q000009:adverse effects / Q000379:methods*; D013552:Swine