Impaired Progression of Cerebral Aneurysms in Interleukin-1β–Deficient Mice

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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-1β (IL-1β) 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-1β in cerebral aneurysm development. Methods— Cerebral aneurysms were experimentally induced in 5-week-old male C57BL/6 mice, IL-1β gene–deficient (IL-1β−/−) mice, and age-matched control B10 mice (wild-type). Their cerebral arteries were dissected and examined histologically and immunohistochemically. Results— IL-1β 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-1β−/− and wild-type mice, but the percentage of advanced aneurysm change was significantly larger in wild-type animals. Furthermore, in IL-1β−/− 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-1β−/− mice compared with wild-type animals. Conclusions— IL-1β is important for the progression of cerebral aneurysms in a mouse model. Disruption of the IL-1β gene results in the reduced incidence of mature experimental cerebral aneurysms.