CNS-associated macrophages contribute to intracerebral aneurysm pathophysiology.
CNS-associated macrophages
Intracerebral aneurysms
MRI
Middle cerebral artery
Vascular inflammation
Journal
Acta neuropathologica communications
ISSN: 2051-5960
Titre abrégé: Acta Neuropathol Commun
Pays: England
ID NLM: 101610673
Informations de publication
Date de publication:
18 Mar 2024
18 Mar 2024
Historique:
received:
17
12
2023
accepted:
06
03
2024
medline:
19
3
2024
pubmed:
19
3
2024
entrez:
19
3
2024
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 38500201
doi: 10.1186/s40478-024-01756-5
pii: 10.1186/s40478-024-01756-5
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
43Subventions
Organisme : H2020 Marie Skłodowska-Curie Actions
ID : No. 813294
Informations de copyright
© 2024. The Author(s).
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