This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Morimoto, M. Articles by Hashimoto, N. Search for Related Content PubMed PubMed Citation Articles by Morimoto, M. Articles by Hashimoto, N. Pubmed/NCBI databases Medline Plus Health Information Brain Aneurysm Related Collections Remodeling Animal models of human disease Cerebral Aneurysm, AVM, & Subarachnoid hemorrhage

(Stroke. 2002;33:1911.)
© 2002 American Heart Association, Inc.

Original Contributions

Mouse Model of Cerebral Aneurysm

Experimental Induction by Renal Hypertension and Local Hemodynamic Changes

Masafumi Morimoto, MD; Susumu Miyamoto, MD; Akira Mizoguchi, MD; Noriaki Kume, MD; Toru Kita, MD Nobuo Hashimoto, MD

From the Departments of Neurosurgery (M.M., S.M., N.H.), Geriatric Medicine (N.K., T.K.), and Anatomy (A.M.), Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Correspondence to Nobuo Hashimoto, MD, Department of Neurosurgery, Kyoto University, Graduate School of Medicine, 54 Kawahara, Shogoin, Sakyo-ku, Kyoto, 606-8507 Japan. E-mail nhashimo{at}kuhp.kyoto-u.ac.jp

Background and Purpose— Rupture of cerebral aneurysm (CA) is the major cause of subarachnoid hemorrhage. Molecular mechanisms of this disease, however, remain unknown. To make possible genetic analysis of CA formation with genetically altered mice, we have successfully established a mouse model of saccular CA that recapitulates the essential features of human saccular CA.

Methods— In C57black/6 male mice, various stages of CAs were experimentally induced at the right anterior cerebral artery–olfactory artery bifurcations by ligations of left common carotid arteries and posterior branches of bilateral renal arteries with high salt diet. Both light and electron microscopic studies were performed with the longitudinal sections of anterior cerebral artery–olfactory artery bifurcations.

Results— In the treated group, various aneurysmal changes were detected in 14 of 18 mice. On the other hand, in the control group, no aneurysmal changes were found in 15 mice. In microscopic studies, aneurysmal changes were shown to include mainly fragmentation of internal elastic lamina, thinning of the smooth muscle cell layer, and degeneration of adventitial tissue, which were very similar to critical changes in human saccular CA.

Conclusions— This mouse model of CA will be useful for studying the effects of complex determinants on CA formation and makes it possible to understand the pathogenesis of CA at the molecular level.

Key Words: cerebral aneurysm • genetics • hemodynamics • hypertension, renal • mice

This article has been cited by other articles:

				Y. Nuki, T.-L. Tsou, C. Kurihara, M. Kanematsu, Y. Kanematsu, and T. Hashimoto Elastase-Induced Intracranial Aneurysms in Hypertensive Mice Hypertension, December 1, 2009; 54(6): 1337 - 1344. [Abstract] [Full Text] [PDF]

				C.-J. Chang, C.-C. Chen, L.-A. Hsu, G.-J. Chang, Y.-H. Ko, C.-F. Chen, M.-Y. Chen, S.-H. Yang, and J.-H. S. Pang Degradation of the Internal Elastic Laminae in Vein Grafts of Rats with Aortocaval Fistulae: Potential Impact on Graft Vasculopathy Am. J. Pathol., May 1, 2009; 174(5): 1837 - 1846. [Abstract] [Full Text] [PDF]

				T. Aoki, H. Kataoka, R. Ishibashi, K. Nozaki, K. Egashira, and N. Hashimoto Impact of Monocyte Chemoattractant Protein-1 Deficiency on Cerebral Aneurysm Formation Stroke, March 1, 2009; 40(3): 942 - 951. [Abstract] [Full Text] [PDF]

				L. Gao, Y. Hoi, D. D. Swartz, J. Kolega, A. Siddiqui, and H. Meng Nascent Aneurysm Formation at the Basilar Terminus Induced by Hemodynamics Stroke, July 1, 2008; 39(7): 2085 - 2090. [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]

				T. Aoki, H. Kataoka, T. Moriwaki, K. Nozaki, and N. Hashimoto Role of TIMP-1 and TIMP-2 in the Progression of Cerebral Aneurysms Stroke, August 1, 2007; 38(8): 2337 - 2345. [Abstract] [Full Text] [PDF]

				S. Tateshima, K. Tanishita, H. Omura, J.P. Villablanca, and F. Vinuela Intra-Aneurysmal Hemodynamics during the Growth of an Unruptured Aneurysm: In Vitro Study Using Longitudinal CT Angiogram Database AJNR Am. J. Neuroradiol., April 1, 2007; 28(4): 622 - 627. [Abstract] [Full Text] [PDF]

				T. Aoki, H. Kataoka, M. Morimoto, K. Nozaki, and N. Hashimoto Macrophage-Derived Matrix Metalloproteinase-2 and -9 Promote the Progression of Cerebral Aneurysms in Rats Stroke, January 1, 2007; 38(1): 162 - 169. [Abstract] [Full Text] [PDF]

				T. Moriwaki, Y. Takagi, N. Sadamasa, T. Aoki, K. Nozaki, and N. Hashimoto Impaired Progression of Cerebral Aneurysms in Interleukin-1{beta}-Deficient Mice Stroke, March 1, 2006; 37(3): 900 - 905. [Abstract] [Full Text] [PDF]

				N. Sadamasa, K. Nozaki, and N. Hashimoto Disruption of Gene for Inducible Nitric Oxide Synthase Reduces Progression of Cerebral Aneurysms Stroke, December 1, 2003; 34(12): 2980 - 2984. [Abstract] [Full Text] [PDF]

				S. Wills, A. Ronkainen, M. van der Voet, H. Kuivaniemi, K. Helin, E. Leinonen, J. Frosen, M. Niemela, J. Jaaskelainen, J. Hernesniemi, et al. Familial Intracranial Aneurysms: An Analysis of 346 Multiplex Finnish Families Stroke, June 1, 2003; 34(6): 1370 - 1374. [Abstract] [Full Text] [PDF]