Development of an angiogenesis animal model featuring brain arteriovenous malformation histological characteristics.

Abstract

Angiogenesis has a key role in the formation and evolution of brain arteriovenous malformations (AVMs). Numerous models have been developed aiming to recreate configuration of brain AVMs. To develop an animal model sharing the same pathological characteristics as human brain AVMs. Ten pigs were divided into two groups. Five animals underwent endovascular left common carotid artery (CCA) and external carotid artery (ECA) occlusion and five animals served as controls. DSA, associated with 3D-rotational angiography, was performed at day 0 and at 3 months in both groups. The volume of the retia was calculated. Vascular endothelial growth factor (VEGF)-A serum levels were measured in both groups at the same time intervals. Finally, the animals were sacrificed at 3 months and the retia were harvested for pathological and immunohistochemistry examinations. At 3 months, a significantly higher rete volume was seen in group A than in group B (2.92±0.33 mL vs 1.87±0.69 mL, respectively; p=0.016). There was a trend for increased VEGF-A levels in group A at 3 months. In the occlusion group, histological findings showed significant reduction of media thickness and disrupted internal elastic lamina; immunohistochemistry findings showed strong reactivity for VEGF receptors and interleukin 6. Unilateral endovascular occlusion of the CCA-ECA results in angiogenesis triggering of the rete mirabile with both significant augmentation of the rete volume and histological evidence of pro-angiogenic stimulation.