Background Intracranial aneurysms represent a significant health concern and are poorly understood despite decades of research. Our study focused on understanding temporal patterns of endothelial cell distribution in different spatial locations within the aneurysm early after creation in a rabbit model.
Methods Elastase induced saccular aneurysms were created in rabbits and harvested on day 1 (n=3) and after 2 (n=5), 4 (n=4), 8 (n=5), and 12 (n=6) weeks. Sham operated controls (n=3) were harvested on the same day. Aneurysm and control tissue samples were subjected to en face whole mount CD31 staining for endothelial cells. Semiquantitative scoring was performed on the basis of endothelial coverage of the vessel wall (proximal, middle, and distal portions of the aneurysm dome). Mixed effects models were used to assess the effect of time and aneurysm section on endothelial coverage.
Results Aneurysmal segments were near completely de-endothelialized at 4 and 8 weeks but had re-endothelialized by 12 weeks. Compared with controls, aneurysms at all time points showed decreased endothelialization, but the difference was only significant compared with the 4 and 8 week groups. Both time (P=0.03) and aneurysm section (P=0.07) were significantly associated with the degree of endothelialization. Proximal locations showed increased endothelialization compared with distal locations (P=0.03).
Conclusion In experimental aneurysms of rabbits, endothelial cells regress during the first month after creation, followed by ascending re-endothelialization that stays incomplete. These findings suggest that re-population of endothelial cells comes from resident cells in the adjacent parent artery and that deranged hemodynamics may affect full reconstitution of endothelial cells long term.
- vessel wall
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Contributors PKP and DD contributed to tissue processing, slides staining, interpretation of the data, and drafting of the manuscript. Y-HD contributed to the aneurysm model creation. TG contributed to the statistics of the study. DFK and KR contributed to the conception and design of the study, and to revision of the article critically for important intellectual content.
Funding This work was supported by grants from the National Institutes of Health awarded to KR (R01.NS076491) and DFK (R21.NS088256). 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.
Correction notice Since this article was first published online the author name Kadirvel Ramanathan has been updated. It has been corrected to read Ramanathan Kadirvel.
Presented at These data were presented at the 14th Annual Meeting of the Society of Neurointerventional Surgery, Colorado Springs, Colorado, July 23-28, 2017.