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Stroke. 2011 Jan;42(1):173-8. doi: 10.1161/STROKEAHA.110.590976. Epub 2010 Nov 24.

Critical roles of macrophages in the formation of intracranial aneurysm.

Author information

1
Department of Anesthesia and Perioperative Care, University of California, San Francisco, San Francisco, CA 94110, USA. hashimot@anesthesia.ucsf.edu

Abstract

BACKGROUND AND PURPOSE:

abnormal vascular remodeling triggered by hemodynamic stresses and inflammation is believed to be a key process in the pathophysiology of intracranial aneurysms. Numerous studies have shown infiltration of inflammatory cells, especially macrophages, into intracranial aneurysmal walls in humans. Using a mouse model of intracranial aneurysms, we tested whether macrophages play critical roles in the formation of intracranial aneurysms.

METHODS:

intracranial aneurysms were induced in adult male mice using a combination of a single injection of elastase into the cerebrospinal fluid and angiotensin II-induced hypertension. Aneurysm formation was assessed 3 weeks later. Roles of macrophages were assessed using clodronate liposome-induced macrophage depletion. In addition, the incidence of aneurysms was assessed in mice lacking monocyte chemotactic protein-1 (CCL2) and mice lacking matrix metalloproteinase-12 (macrophage elastase).

RESULTS:

intracranial aneurysms in this model showed leukocyte infiltration into the aneurysmal wall, the majority of the leukocytes being macrophages. Mice with macrophage depletion had a significantly reduced incidence of aneurysms compared with control mice (1 of 10 versus 6 of 10; P<0.05). Similarly, there was a reduced incidence of aneurysms in mice lacking monocyte chemotactic protein-1 compared with the incidence of aneurysms in wild-type mice (2 of 10 versus 14 of 20, P<0.05). There was no difference in the incidence of aneurysms between mice lacking matrix metalloproteinase-12 and wild-type mice.

CONCLUSIONS:

these data suggest critical roles of macrophages and proper macrophage functions in the formation of intracranial aneurysms in this model.

PMID:
21106959
PMCID:
PMC3021554
DOI:
10.1161/STROKEAHA.110.590976
[Indexed for MEDLINE]
Free PMC Article

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