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.
