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.
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 B10mice (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.
Authors: T Aoki; M Nishimura; T Matsuoka; K Yamamoto; T Furuyashiki; H Kataoka; S Kitaoka; R Ishibashi; A Ishibazawa; S Miyamoto; R Morishita; J Ando; N Hashimoto; K Nozaki; S Narumiya Journal: Br J Pharmacol Date: 2011-07 Impact factor: 8.739
Authors: Robert M Starke; Nohra Chalouhi; Dale Ding; Daniel M S Raper; M Sean Mckisic; Gary K Owens; David M Hasan; Ricky Medel; Aaron S Dumont Journal: Transl Stroke Res Date: 2013-10-10 Impact factor: 6.829