Published Online
on January 26, 2006

A more recent version of this article appeared on March 1, 2006

This Article Full Text (PDF) All Versions of this Article: 37/3/900    most recent 01.STR.0000204028.39783.d9v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Moriwaki, T. Articles by Hashimoto, N. Search for Related Content PubMed PubMed Citation Articles by Moriwaki, T. Articles by Hashimoto, N. Related Collections Cerebrovascular disease/stroke Apoptosis Pathophysiology Gene expression Genetically altered mice Cerebral Aneurysm, AVM, & Subarachnoid hemorrhage Other Vascular biology

Submitted on October 31, 2005
Revised on November 27, 2005
Accepted on December 7, 2005

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

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

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

^* To whom correspondence should be addressed. 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-1 (IL-1) 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-1 in cerebral aneurysm development.

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

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

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

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

This article has been cited by other articles:

				T. Aoki, H. Kataoka, R. Ishibashi, K. Nozaki, R. Morishita, and N. Hashimoto Reduced Collagen Biosynthesis Is the Hallmark of Cerebral Aneurysm: Contribution of Interleukin-1{beta} and Nuclear Factor-{kappa}B Arterioscler Thromb Vasc Biol, July 1, 2009; 29(7): 1080 - 1086. [Abstract] [Full Text] [PDF]

				C. Shi, I. A. Awad, N. Jafari, S. Lin, P. Du, Z. A. Hage, R. Shenkar, C. C. Getch, M. Bredel, H. H. Batjer, et al. Genomics of Human Intracranial Aneurysm Wall Stroke, April 1, 2009; 40(4): 1252 - 1261. [Abstract] [Full Text] [PDF]

				T. Aoki, H. Kataoka, R. Ishibashi, K. Nozaki, and N. Hashimoto Cathepsin B, K, and S Are Expressed in Cerebral Aneurysms and Promote the Progression of Cerebral Aneurysms Stroke, September 1, 2008; 39(9): 2603 - 2610. [Abstract] [Full Text] [PDF]

				T. Aoki, H. Kataoka, R. Ishibashi, K. Nozaki, and N. Hashimoto Simvastatin Suppresses the Progression of Experimentally Induced Cerebral Aneurysms in Rats Stroke, April 1, 2008; 39(4): 1276 - 1285. [Abstract] [Full Text] [PDF]

				T. Aoki, H. Kataoka, M. Shimamura, H. Nakagami, K. Wakayama, T. Moriwaki, R. Ishibashi, K. Nozaki, R. Morishita, and N. Hashimoto NF-{kappa}B Is a Key Mediator of Cerebral Aneurysm Formation Circulation, December 11, 2007; 116(24): 2830 - 2840. [Abstract] [Full Text] [PDF]