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Original research
Development of an angiogenesis animal model featuring brain arteriovenous malformation histological characteristics
  1. Chrysanthi Papagiannaki1,2,
  2. Frédéric Clarençon1,3,
  3. Sébastien Ponsonnard1,4,
  4. Claude Couquet5,
  5. Franck Maizeroi-Eugène6,
  6. Damien Bresson7,
  7. Catherine Yardin1,8,
  8. Charbel Mounayer1,9
  1. 1ERMA (Equipe de Recherche Medicale Appliquée), Limoges University Hospital, Limoges, France
  2. 2Interventional Neuroradiology Department, Rouen University Hospital, Rouen, France
  3. 3Interventional Neuroradiology Department, Pitié-Salpêtrière Hospital, Paris, France
  4. 4Anesthesiology Department, Limoges University Hospital, Limoges, France
  5. 5Haute Vienne Departmental Laboratory for Research and Analysis, Limoges, France
  6. 6Maizeroi-Eugène Society, Paris, France
  7. 7Department of Neurosurgery, Lariboisière University Hospital, Paris, France
  8. 8Department of Histology, Cytology, Cellular Biology and Cytogenetics, Limoges University Hospital, Limoges, France
  9. 9Department of Interventional Neuroradiology, Limoges University Hospital, Limoges, France
  1. Correspondence to Dr Chrysanthi Papagiannaki, CHU Rouen “Charles Nicolle”, Service de Neuroradiologie Vasculaire Interventionnelle, 1 Rue de Germont, Rouen 76000, France; chrisanthi.papa{at}gmail.com

Abstract

Background 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.

Objective To develop an animal model sharing the same pathological characteristics as human brain AVMs.

Materials and methods 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.

Results 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.

Conclusions 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.

  • Arteriovenous Malformation
  • Angiography
  • Vessel Wall

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Footnotes

  • Contributors CP: concept, design and development of the study, acquisition, analysis and interpretation of the data, writing of the article. FC: concept, design and development of the study, statistical analysis, acquisition, analysis and interpretation of the data, critical review of the article. SP, CC, FM-E: development of the study, acquisition, analysis and interpretation of the data. DB: critical review of the article. CY, CM: critical review of the article, analysis and interpretation of the data.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement Any technical detail concerning the creation of the model and the results are available from the corresponding author.