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Stroke. 2006;37:900-905
Published online before print January 26, 2006, doi: 10.1161/01.STR.0000204028.39783.d9
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(Stroke. 2006;37:900.)
© 2006 American Heart Association, Inc.


Original Contributions

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

Takuya Moriwaki, MD; Yasushi Takagi, MD, PhD; Nobutake Sadamasa, MD, PhD; Tomohiro Aoki, MD, PhD; Kazuhiko Nozaki, MD, PhD Nobuo Hashimoto, MD, PhD

From the Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.

Correspondence to Yasushi Takagi, MD, PhD, Department of Neurosurgery, Graduate School of Medicine, Kyoto University, 54 Kawaharacho, Shogoin, Sakyo, Kyoto 606-8507. E-mail ytakagi{at}kuhp.kyoto-u.ac.jp

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-1ß (IL-1ß) 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-1ß in cerebral aneurysm development.

Methods— Cerebral aneurysms were experimentally induced in 5-week-old male C57BL/6 mice, IL-1ß gene–deficient (IL-1ß–/–) mice, and age-matched control B10 mice (wild-type). Their cerebral arteries were dissected and examined histologically and immunohistochemically.

Results— IL-1ß 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-1ß–/– and wild-type mice, but the percentage of advanced aneurysm change was significantly larger in wild-type animals. Furthermore, in IL-1ß–/– 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-1ß–/– mice compared with wild-type animals.

Conclusions— IL-1ß is important for the progression of cerebral aneurysms in a mouse model. Disruption of the IL-1ß gene results in the reduced incidence of mature experimental cerebral aneurysms.


Key Words: animal models • apoptosis • cerebral aneurysm • cerebrovascular disorders • interleukins




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