Topographic distribution of inflammation factors in a healing aneurysm

Journal of Neuroinflammation

Research

Serge Marbacher¹  Jeannine Rey¹  Stefan Wanderer¹  Joshua Hägler¹  Gwendoline Canzanella¹  Lukas Andereggen¹  Basil E. Grüter²  Luca Remonda³  Rainer Grobholz⁴  Hans-Rudolf Widmer⁵  Michael von Gunten⁶  José A. Galvan⁷ 

[1]Department of Neurosurgery, Kantonsspital Aarau, Aarau, Switzerland

[2]Program for Regenerative Neuroscience, Department for BioMedical Research, University of Bern, Bern, Switzerland

[3]Division of Neuroradiology, Department of Radiology, Kantonsspital Aarau, C/o NeuroResearch Office,Tellstrasse 1, 5001, Aarau, Switzerland

[4]Department of Neurosurgery, Kantonsspital Aarau, Aarau, Switzerland

[5]Program for Regenerative Neuroscience, Department for BioMedical Research, University of Bern, Bern, Switzerland

[6]Division of Neuroradiology, Department of Radiology, Kantonsspital Aarau, C/o NeuroResearch Office,Tellstrasse 1, 5001, Aarau, Switzerland

[7]Program for Regenerative Neuroscience, Department for BioMedical Research, University of Bern, Bern, Switzerland

[8]Institute of Pathology, Kantonsspital Aarau, Aarau, Switzerland

[9]Medical Faculty, University of Zurich, Zurich, Switzerland

[10]Program for Regenerative Neuroscience, Department for BioMedical Research, University of Bern, Bern, Switzerland

[11]Program for Regenerative Neuroscience, Department for BioMedical Research, University of Bern, Bern, Switzerland

[12]Institute of Pathology Laenggasse, Ittigen, Switzerland

[13]Translational Research Unit (TRU), Institute of Pathology, University of Bern, Bern, Switzerland

关键词: Endovascular procedures;    Inflammation;    Intracranial aneurysm;    Models;    Animal;    Neointima;   

DOI  :  10.1186/s12974-023-02863-1

 received in 2023-05-23, accepted in 2023-07-26,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundHealing of intracranial aneurysms following endovascular treatment relies on the organization of early thrombus into mature scar tissue and neointima formation. Activation and deactivation of the inflammation cascade plays an important role in this process. In addition to timely evolution, its topographic distribution is hypothesized to be crucial for successful aneurysm healing.MethodsDecellularized saccular sidewall aneurysms were created in Lewis rats and coiled. At follow-up (after 3 days (n = 16); 7 days (n = 19); 21 days (n = 8)), aneurysms were harvested and assessed for healing status. In situ hybridization was performed for soluble inflammatory markers (IL6, MMP2, MMP9, TNF-α, FGF23, VEGF), and immunohistochemical analysis to visualize inflammatory cells (CD45, CD3, CD20, CD31, CD163, HLA-DR). These markers were specifically documented for five regions of interest: aneurysm neck, dome, neointima, thrombus, and adjacent vessel wall.ResultsCoiled aneurysms showed enhanced patterns of thrombus organization and neointima formation, whereas those without treatment demonstrated heterogeneous patterns of thrombosis, thrombus recanalization, and aneurysm growth (p = 0.02). In coiled aneurysms, inflammation markers tended to accumulate inside the thrombus and in the neointima (p < 0.001). Endothelial cells accumulated directly in the neointima (p < 0.0001), and their presence was associated with complete aneurysm healing.ConclusionThe presence of proinflammatory cells plays a crucial role in aneurysm remodeling after coiling. Whereas thrombus organization is hallmarked by a pronounced intra-thrombotic inflammatory reaction, neointima maturation is characterized by direct invasion of endothelial cells. Knowledge concerning topographic distribution of regenerative inflammatory processes may pave the way for future treatment modalities which enhance aneurysm healing after endovascular therapy.

【 授权许可】

CC BY   
© The Author(s) 2023

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