Impaired progression of cerebral aneurysms in interleukin-1beta-deficient mice.

Abstract:

BACKGROUND AND PURPOSE:Subarachnoid hemorrhage caused by cerebral aneurysm rupture remains a life-threatening emergency despite advances in treatment. However, the mechanisms underlying aneurysm initiation, progression, and rupture remain unclear. We developed a method to induce experimental cerebral aneurysms in rats, monkeys, and mice. Interleukin-1beta (IL-1beta) is a key inflammatory mediator, and it is thought to be a promising target for the treatment of inflammatory diseases. In the present study, we examined the role of IL-1beta in cerebral aneurysm development. METHODS:Cerebral aneurysms were experimentally induced in 5-week-old male C57BL/6 mice, IL-1beta gene-deficient (IL-1beta-/-) mice, and age-matched control B10 mice (wild-type). Their cerebral arteries were dissected and examined histologically and immunohistochemically. RESULTS:IL-1beta was expressed in vascular media in mice at an early stage of aneurysmal models' cerebral arteries. No differences were seen in the rate of aneurysm development between IL-1beta-/- and wild-type mice, but the percentage of advanced aneurysm change was significantly larger in wild-type animals. Furthermore, in IL-1beta-/- mice, increased caspase-1 expression was seen compared with wild-type animals. Additionally, the number of apoptotic cells assessed by single-stranded DNA immunoreactivity and TUNEL was significantly reduced in IL-1beta-/- mice compared with wild-type animals. CONCLUSIONS:IL-1beta is important for the progression of cerebral aneurysms in a mouse model. Disruption of the IL-1beta gene results in the reduced incidence of mature experimental cerebral aneurysms.

journal_name

Stroke

journal_title

Stroke

authors

Moriwaki T,Takagi Y,Sadamasa N,Aoki T,Nozaki K,Hashimoto N

doi

10.1161/01.STR.0000204028.39783.d9

subject

Has Abstract

pub_date

2006-03-01 00:00:00

pages

900-5

issue

3

eissn

0039-2499

issn

1524-4628

pii

01.STR.0000204028.39783.d9

journal_volume

37

pub_type

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