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Stereotactic radiosurgery of the rete mirabile in swine: a longitudinal study of histopathological changes
Reza Jahan1, Timothy D Solberg, Daniel Lee
1Division 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
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.
Conclusion:
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.
Insights
Stereotactic radiosurgery causes progressive vessel occlusion in swine rete mirabile due to smooth muscle cell proliferation and collagen deposition. This study clarifies the histopathological changes following radiation treatment for arteriovenous malformations.
Area of Science:
- Vascular Biology
- Radiation Oncology
- Histopathology
Background:
- Stereotactic radiosurgery is a key treatment for brain arteriovenous malformations.
- The precise mechanisms of vessel occlusion post-radiosurgery require further elucidation.
Purpose of the Study:
- To investigate the histopathological alterations in the swine rete mirabile following stereotactic radiosurgery.
- To understand the cellular and matrix changes contributing to vessel occlusion.
Main Methods:
- Histological, immunohistochemical, and morphometric analyses were performed on swine rete mirabile tissue.
- Samples were collected from both nonradiated control and radiated groups at various time points (3, 6, and 9 months).
Main Results:
- Radiated vessels exhibited progressive intimal hyperplasia and luminal narrowing over time.
- Proliferating smooth muscle cells and extracellular collagen Type IV were identified in the intima and adventitia of radiated vessels.
- Control vessels showed minimal changes, indicating radiation-induced effects.
Conclusions:
- Stereotactic radiosurgery induces an intimal response characterized by smooth muscle cell migration, proliferation, and collagen synthesis, leading to vessel occlusion.
- These changes are likely mediated by cytokine pathways, warranting further investigation into molecular mechanisms.
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