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Increased macrophage M2/M1 ratio is associated with intracranial aneurysm rupture

  • Original Article - Vascular Neurosurgery - Aneurysm
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Abstract

Purpose

Intracranial aneurysm (IA) rupture results in one of the most severe forms of stroke, with severe neurological sequelae. Inflammation appears to drive aneurysm formation and progression with macrophages playing a key role in this process. However, less is known about their involvement in aneurysm rupture. This study is aimed at demonstrating how relationship between the M1 (pro-inflammatory) and M2 (reparative) macrophage subtypes affect an aneurysm’s structure resulting in its rupture.

Methods

Forty-one saccular aneurysm wall samples were collected during surgery including 13 ruptured and 28 unruptured aneurysm sacs. Structural changes were evaluated using histological staining. Macrophages in the aneurysm wall were quantified and defined as M1 and M2 using HLA-DR and CD163 antibodies. Aneurysm samples were divided into four groups according to the structural changes and the M2/1 ratio. Data were analyzed using the Mann–Whitney U test.

Results

This study has demonstrated an association between the severity of structural changes of an aneurysm with inflammatory cell infiltration within its wall and subsequent aneurysm rupture. More severe morphological changes and a significantly higher number of inflammatory cells were observed in ruptured IAs (p < 0.001). There was a prevalence of M2 macrophage subtypes within the wall of ruptured aneurysms (p < 0.001). A subgroup of unruptured IAs with morphological and inflammatory changes similar to ruptured IAs was observed. The common feature of this subgroup was the presence of an intraluminal thrombus.

Conclusions

The degree of inflammatory cell infiltration associated with a shift in macrophage phenotype towards M2 macrophages could play an important role in structural changes of the aneurysm wall leading to its rupture.

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Acknowledgements

We would like to acknowledge Dr. Jan Lodin, a native speaker, for his assistance in proofreading the manuscript.

Funding

The study was supported by the Grants of the Ministry of Health of Czech Republic (NU22-08–00124, NV19-04–00270), and the Internal Grant Agency of the Krajská zdravotní (IGA-KZ-2019–1-11). The figures were created (Fig. 3) and arranged (Fig. 2 and Fig. 4) with BioRender.com.

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Author notes

  1. Mária Hundža Stratilová and Miroslav Koblížek contributed equally to this work.

Authors and Affiliations

  1. Department of Neurosurgery, J. E. Purkyne University, Masaryk Hospital, Sociální péče 3316/12A, 400 13, Ústí Nad Labem, Czech Republic

    Mária Hundža Stratilová, Martin Sameš & Aleš Hejčl

  2. Department of Pathology and Molecular Medicine, 2nd Faculty of Medicine, Charles University, and Motol University Hospital, Prague, Czech Republic

    Mária Hundža Stratilová, Miroslav Koblížek & Josef Zámečník

  3. Department of Neurosurgery and Neurooncology, Military University Hospital and Charles University, First Medical Faculty, Prague, Czech Republic

    Anna Štekláčová & Vladimír Beneš

  4. International Clinical Research Center, St. Anne’s Hospital, Brno, Czech Republic

    Aleš Hejčl

  5. Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic

    Aleš Hejčl

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  1. Mária Hundža Stratilová
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Correspondence to Aleš Hejčl.

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The approval of the Ethics Committee of Masaryk Hospital, Ústí nad Labem (Reference Number: 238/59), was obtained on 22 June 2016.

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Stratilová, M.H., Koblížek, M., Štekláčová, A. et al. Increased macrophage M2/M1 ratio is associated with intracranial aneurysm rupture. Acta Neurochir 165, 177–186 (2023). https://doi.org/10.1007/s00701-022-05418-0

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