Skip to main content

Translational Research Using a Mouse Model of Intracranial Aneurysm

Translational Stroke Research volume 5, pages 248–251 (2014)Cite this article

Abstract

We have developed a mouse model of intracranial aneurysm that recapitulates key features of human intracranial aneurysms. In this model, spontaneous aneurysmal rupture occurs with a predictable time course. Aneurysmal rupture in this model can be easily detected by assessing neurological symptoms. Similar to human intracranial aneurysms, intracranial aneurysms in this model show an infiltration with inflammatory cells. This mouse model can be used to study the mechanisms and the potential preventive treatments for aneurysmal rupture.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

Fig. 1

References

  1. Brisman JL, Song JK, Newell DW. Cerebral aneurysms. N Engl J Med. 2006;355(9):928–39. doi:10.1056/NEJMra052760.

    CAS  PubMed  Article  Google Scholar 

  2. Vlak MH, Algra A, Brandenburg R, Rinkel GJ. Prevalence of unruptured intracranial aneurysms, with emphasis on sex, age, comorbidity, country, and time period: a systematic review and meta-analysis. Lancet Neurol. 2011;10(7):626–36.

    PubMed  Article  Google Scholar 

  3. Berman MF, Solomon RA, Mayer SA, Johnston SC, Yung PP. Impact of hospital-related factors on outcome after treatment of cerebral aneurysms. Stroke. 2003;34(9):2200–7. doi:10.1161/01.STR.0000086528.32334.06.

    PubMed  Article  Google Scholar 

  4. Zacharia BE, Ducruet AF, Hickman ZL, Grobelny BT, Badjatia N, Mayer SA, et al. Technological advances in the management of unruptured intracranial aneurysms fail to improve outcome in New York state. Stroke. 2011;42(10):2844–9. doi:10.1161/STROKEAHA.111.619767.

    PubMed  Article  Google Scholar 

  5. Gabriel RA, Kim H, Sidney S, McCulloch CE, Singh V, Johnston SC, et al. Ten-year detection rate of brain arteriovenous malformations in a large, multiethnic, defined population. Stroke. 2010;41(1):21–6. doi:10.1161/STROKEAHA.109.566018.

    PubMed Central  PubMed  Article  Google Scholar 

  6. Rao VM, Parker L, Levin DC, Sunshine J, Bushee G. Use trends and geographic variation in neuroimaging: nationwide medicare data for 1993 and 1998. AJNR Am J Neuroradiol. 2001;22(9):1643–9.

    CAS  PubMed  Google Scholar 

  7. Schievink WI. Intracranial aneurysms. N Engl J Med. 1997;336(1):28–40.

    CAS  PubMed  Article  Google Scholar 

  8. Bederson JB, Awad IA, Wiebers DO, Piepgras D, Haley Jr EC, Brott T, et al. Recommendations for the management of patients with unruptured intracranial aneurysms: a statement for healthcare professionals from the Stroke Council of the American Heart Association. Stroke. 2000;31(11):2742–50.

    CAS  PubMed  Article  Google Scholar 

  9. Raaymakers TW, Rinkel GJ, Limburg M, Algra A. Mortality and morbidity of surgery for unruptured intracranial aneurysms: a meta-analysis. Stroke. 1998;29(8):1531–8.

    CAS  PubMed  Article  Google Scholar 

  10. Wiebers DO, Whisnant JP, Huston 3rd J, Meissner I, Brown Jr RD, Piepgras DG, et al. Unruptured intracranial aneurysms: natural history, clinical outcome, and risks of surgical and endovascular treatment. Lancet. 2003;362(9378):103–10.

    PubMed  Article  Google Scholar 

  11. Nuki Y, Tsou TL, Kurihara C, Kanematsu M, Kanematsu Y, Hashimoto T. Elastase-induced intracranial aneurysms in hypertensive mice. Hypertension. 2009;54(6):1337–44. doi:10.1161/HYPERTENSIONAHA.109.138297.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  12. Kanematsu Y, Kanematsu M, Kurihara C, Tada Y, Tsou TL, van Rooijen N, et al. Critical roles of macrophages in the formation of intracranial aneurysm. Stroke. 2011;42(1):173–8. doi:10.1161/STROKEAHA.110.590976.

    PubMed Central  PubMed  Article  Google Scholar 

  13. Tada Y, Kanematsu Y, Kanematsu M, Nuki Y, Liang EI, Wada K, et al. A mouse model of intracranial aneurysm: technical considerations. Acta Neurochir Suppl. 2011;111:31–5. doi:10.1007/978-3-7091-0693-8_6.

    PubMed Central  PubMed  Article  Google Scholar 

  14. Connolly Jr ES, Choudhri TF, Mack WJ, Mocco J, Spinks TJ, Slosberg J, et al. Influence of smoking, hypertension, and sex on the phenotypic expression of familial intracranial aneurysms in siblings. Neurosurgery. 2001;48(1):64–8.

    PubMed  Google Scholar 

  15. Bonita R. Cigarette smoking, hypertension and the risk of subarachnoid hemorrhage: a population-based case-control study. Stroke. 1986;17(5):831–5.

    CAS  PubMed  Article  Google Scholar 

  16. Morimoto M, Miyamoto S, Mizoguchi A, Kume N, Kita T, Hashimoto N. Mouse model of cerebral aneurysm: experimental induction by renal hypertension and local hemodynamic changes. Stroke. 2002;33(7):1911–5.

    PubMed  Article  Google Scholar 

  17. Cajander S, Hassler O. Enzymatic destruction of the elastic lamella at the mouth of cerebral berry aneurysm? An ultrastructural study with special regard to the elastic tissue. Acta Neurol Scand. 1976;53(3):171–81.

    CAS  PubMed  Article  Google Scholar 

  18. Weiss D, Taylor WR. Deoxycorticosterone acetate salt hypertension in apolipoprotein E−/− mice results in accelerated atherosclerosis: the role of angiotensin II. Hypertension. 2008;51(2):218–24.

    CAS  PubMed  Article  Google Scholar 

  19. Kanematsu Y, Kanematsu M, Kurihara C, Tsou TL, Nuki Y, Liang EI, et al. Pharmacologically induced thoracic and abdominal aortic aneurysms in mice. Hypertension. 2010;55(5):1267–74. doi:10.1161/HYPERTENSIONAHA.109.140558.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  20. Makino H, Tada Y, Wada K, Liang EI, Chang M, Mobashery S, et al. Pharmacological stabilization of intracranial aneurysms in mice: a feasibility study. Stroke. 2012;43(9):2450–6. doi:10.1161/STROKEAHA.112.659821.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  21. Huang Z, Huang PL, Panahian N, Dalkara T, Fishman MC, Moskowitz MA. Effects of cerebral ischemia in mice deficient in neuronal nitric oxide synthase. Science. 1994;265(5180):1883–5.

    CAS  PubMed  Article  Google Scholar 

  22. Yang G, Chan PH, Chen J, Carlson E, Chen SF, Weinstein P, et al. Human copper–zinc superoxide dismutase transgenic mice are highly resistant to reperfusion injury after focal cerebral ischemia. Stroke. 1994;25(1):165–70.

    PubMed  Article  Google Scholar 

  23. Chan PH. Oxygen radicals in focal cerebral ischemia. Brain Pathol. 1994;4(1):59–65.

    CAS  PubMed  Article  Google Scholar 

  24. Jeon H, Ai J, Sabri M, Tariq A, Shang X, Chen G, et al. Neurological and neurobehavioral assessment of experimental subarachnoid hemorrhage. BMC Neurosci. 2009;10:103. doi:10.1186/1471-2202-10-103.

    PubMed Central  PubMed  Article  Google Scholar 

  25. Hasan DM, Mahaney KB, Brown Jr RD, Meissner I, Piepgras DG, Huston J, et al. Aspirin as a promising agent for decreasing incidence of cerebral aneurysm rupture. Stroke. 2011;42(11):3156–62. doi:10.1161/STROKEAHA.111.619411.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  26. Tymianski M. Aspirin as a promising agent for decreasing incidence of cerebral aneurysm rupture. Stroke. 2011;42(11):3003–4. doi:10.1161/STROKEAHA.111.626762.

    PubMed  Article  Google Scholar 

  27. Hasan D, Hashimoto T, Kung D, Macdonald RL, Winn HR, Heistad D. Upregulation of cyclooxygenase-2 (COX-2) and microsomal prostaglandin E2 synthase-1 (mPGES-1) in wall of ruptured human cerebral aneurysms: preliminary results. Stroke. 2012;43(7):1964–7. doi:10.1161/STROKEAHA.112.655829.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

Download references

Acknowledgments

The project described was supported by grant numbers R01NS055876 (TH) and R01NS082280 (TH) from the National Institute of Neurological Disorders and Stroke (NIH/NINDS) and the Brain Aneurysm Foundation Shirley Dudek Demmer Chair of Research (KS). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Neurological Disorders and Stroke, the National Institutes of Health, or the Brain Aneurysm Foundation.

Conflict of Interest

None

Author information

Affiliations

  1. Department of Anesthesia and Perioperative Care, University of California, San Francisco, 1001 Potrero Avenue, No. 3C-38, San Francisco, CA, 94110, USA

    Kosuke Wada, Kenji Shimada, Fumiaki Shikata, Atsushi Kuwabara & Tomoki Hashimoto

  2. Department of Anesthesia and Perioperative Care, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu City, Shizuoka, 431-3192, Japan

    Hiroshi Makino

Authors
  1. Kosuke Wada
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hiroshi Makino
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kenji Shimada
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Fumiaki Shikata
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Atsushi Kuwabara
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Tomoki Hashimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tomoki Hashimoto.

Additional information

Kosuke Wada and Hiroshi Makino contributed equally to the project.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Wada, K., Makino, H., Shimada, K. et al. Translational Research Using a Mouse Model of Intracranial Aneurysm. Transl. Stroke Res. 5, 248–251 (2014). https://doi.org/10.1007/s12975-013-0296-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12975-013-0296-8

Keywords

  • Intracranial aneurysms
  • Animal model
  • Inflammation