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Original research
Rabbit aneurysm models mimic histologic wall types identified in human intracranial aneurysms
  1. Shunli Wang1,2,
  2. Daying Dai1,
  3. Praveen Kolumam Parameswaran1,
  4. Ramanathan Kadirvel1,
  5. Yong-Hong Ding1,
  6. Anne M Robertson3,
  7. David F Kallmes1
  1. 1 Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA
  2. 2 Department of Pathology, Shanghai East Hospital, Tongji University, Shanghai, China
  3. 3 Center for Biological Imaging, University of Pittsburgh, Pittsburgh, USA
  1. Correspondence to Dr Daying Dai, Department of Radiology, Mayo Clinic, 55905, Rochester, Minnesota, USA; dai.daying{at}


Background Semiquantitative scales correlate histopathologic findings in the walls of human aneurysms with rupture status.

Objective To apply a semiquantitative scale to the rabbit elastase-induced aneurysm model to determine whether rabbit histologic types mimic the full range of histologic subtypes of humans.

Materials and methods Twenty-seven elastase-induced female rabbit aneurysms were studied, harvested at 2 weeks (n=5) and 12 weeks (n=22). Paraffin-embedded sections received hematoxylin-eosin and Verhoeff-Van Gieson staining. Immunohistochemistry was performed for α-smooth muscle actin and CD31 for endothelial cells. A semiquantitative scale was used for scoring based on human aneurysm tissue, divided into four subtypes according to cellular and extracellular matrix findings: type A, linear organized smooth muscle cells (SMCs) and intact endothelium; type B, thickened wall with disorganized, proliferating SMCs; type C, thick, collagenized and hypocellular wall with or without organizing thrombosis, and type D, extremely thin, hypocellular wall. Separate scoring was performed of the aneurysm neck and proximal and distal zones.

Results Findings compatible with all subtypes of human aneurysm tissue were identified. Types A and C were found in 13 (48%) and 11 (41%) of 27 aneurysms and in the proximal and distal wall at both time points. Type B was found in 16 aneurysms (59%), exclusively at the neck at both time points; type D, in 14 aneurysms (52%), exclusively at proximal and distal zones of 12-week aneurysms.

Conclusions The wall of elastase-induced rabbit aneurysm demonstrates histologic findings similar to the four categories of human cerebral aneurysms based on cellular and extracellular wall content.

  • Intracranial aneurysms
  • animal model
  • histological subtypes

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  • Contributors Y-HD contributed to the aneurysm model creation. SW, DD, and PKP contributed to tissue processing, slides staining, interpretation of data, and drafting of the manuscript. RK, AMR, and DFK contributed to the conception and design of the study and to revision of the article critically for important intellectual content.

  • Funding This study was supported by funds from the National Institutes of Health under grants R01NS076491, R01NS042646, and R21NS088256. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

  • Competing interests None declared.

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

  • Data sharing statement All authors have read the manuscript and have approved its submission. All authors have access to the raw data.

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