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CNS-associated macrophages contribute to intracerebral aneurysm pathophysiology.

Authors :
Glavan, Martina
Jelic, Ana
Levard, Damien
Frösen, Juhana
Keränen, Sara
Franx, Bart A. A.
Bras, Ana-Rita
Louet, Estelle R.
Dénes, Ádám
Merlini, Mario
Vivien, Denis
Rubio, Marina
Source :
Acta Neuropathologica Communications. 3/18/2024, Vol. 12 Issue 1, p1-23. 23p.
Publication Year :
2024

Abstract

Intracerebral aneurysms (IAs) are pathological dilatations of cerebral arteries whose rupture leads to subarachnoid hemorrhage, a significant cause of disability and death. Inflammation is recognized as a critical contributor to the formation, growth, and rupture of IAs; however, its precise actors have not yet been fully elucidated. Here, we report CNS-associated macrophages (CAMs), also known as border-associated macrophages, as one of the key players in IA pathogenesis, acting as critical mediators of inflammatory processes related to IA ruptures. Using a new mouse model of middle cerebral artery (MCA) aneurysms we show that CAMs accumulate in the IA walls. This finding was confirmed in a human MCA aneurysm obtained after surgical clipping, together with other pathological characteristics found in the experimental model including morphological changes and inflammatory cell infiltration. In addition, in vivo longitudinal molecular MRI studies revealed vascular inflammation strongly associated with the aneurysm area, i.e., high expression of VCAM-1 and P-selectin adhesion molecules, which precedes and predicts the bleeding extent in the case of IA rupture. Specific CAM depletion by intracerebroventricular injection of clodronate liposomes prior to IA induction reduced IA formation and rupture rate. Moreover, the absence of CAMs ameliorated the outcome severity of IA ruptures resulting in smaller hemorrhages, accompanied by reduced neutrophil infiltration. Our data shed light on the unexplored role of CAMs as main actors orchestrating the progression of IAs towards a rupture-prone state. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
20515960
Volume :
12
Issue :
1
Database :
Academic Search Index
Journal :
Acta Neuropathologica Communications
Publication Type :
Academic Journal
Accession number :
176119908
Full Text :
https://doi.org/10.1186/s40478-024-01756-5