title: Stereotactic radiosurgery of the rete mirabile in swine: a longitudinal study of histopathological changes.
abstract: 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.
authors.affiliation: 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
authors.forename: Reza
authors.initials: R
authors.lastname: Jahan
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Solberg
authors.forename: Daniel
authors.initials: D
authors.lastname: Lee
authors.forename: Paul
authors.initials: P
authors.lastname: Medin
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tateshima
authors.forename: James
authors.initials: J
authors.lastname: Sayre
authors.forename: Antonio
authors.initials: A
authors.lastname: De Salles
authors.forename: Harry V
authors.initials: HV
authors.lastname: Vinters
authors.forename: Fernando
authors.initials: F
authors.lastname: Vinuela
mesh_terms: 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