Abstract
The mortality rate for subarachnoid hemorrhage from ruptured cerebral aneurysms (CAs) is approximately 50 %. Unruptured aneurysms are present in 2–5 % of adults; their reported annual rupture rate is about 0.5–1.0 %. The pathogenesis of CAs remains to be elucidated. However, there are limitations in CA research; human specimens usually consist of the aneurysmal fundus and do not reflect the pathology of the CA and there are no reliable, reproducible animal models of CAs.
To investigate the formation, structure change, and rupture of the aneurysmal wall we added oophorectomy to Hashimoto’s rat model and established a highly reproducible CA model in rats. Because CAs often arise in postmenopausal women, the rats were subjected to estrogen deficiency, hemodynamic changes, and renal hypertension and fed a high-salt diet.
Here we describe our surgical procedures to induce CA in female rats and present a potential pharmacological treatment to attenuate aneurysm formation. Our rat model yields a better understanding of the pathological mechanisms underlying the formation of aneurysms and provides a means to assess the possibility of medicinal treatments.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Harada K, Fukuyama K, Shirouzu T, Ichinose M, Fujimura H, Kakumoto K, Yamanaga Y. Prevalence of unruptured intracranial aneurysms in healthy asymptomatic Japanese adults: differences in gender and age. Acta Neurochir (Wien). 2013;155:2037–43.
Iwamoto H, Kiyohara Y, Fujishima M, Kato I, Nakayama K, Sueishi K, Tsuneyoshi M. Prevalence of intracranial saccular aneurysms in a Japanese community based on a consecutive autopsy series during a 30-year observation period. The Hisayama study. Stroke. 1999;30:1390–5.
Hamdan A, Barnes J, Mitchell P. Subarachnoid hemorrhage and the female sex: analysis of risk factors, aneurysm characteristics, and outcomes. J Neurosurg. 2014;121:1367–73.
Hashimoto N, Handa H, Hazama F. Experimentally induced cerebral aneurysms in rats. Surg Neurol. 1978;10:3–8.
Handa H, Hashimoto N, Nagata I, Hazama F. Saccular cerebral aneurysms in rats: a newly developed animal model of the disease. Stroke. 1983;14:857–66.
Austin GM, Schievink W, Williams R. Controlled pressure-volume factors in the enlargement of intracranial aneurysms. Neurosurgery. 1989;24:722–30.
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;33:1911–5.
Tamura T, Jamous MA, Kitazato KT, Yagi K, Tada Y, Uno M, Nagahiro S. Endothelial damage due to impaired nitric oxide bioavailability triggers cerebral aneurysm formation in female rats. J Hypertens. 2009;27:1284–92.
Yagi K, Tada Y, Kitazato KT, Tamura T, Satomi J, Nagahiro S. Ibudilast inhibits cerebral aneurysms by down-regulating inflammation-related molecules in the vascular wall of rats. Neurosurgery. 2010;66:551–9.
Tada Y, Yagi K, Kitazato KT, Tamura T, Kinouchi T, Shimada K, Matsushita N, Nakajima N, Satomi J, Kageji T, Nagahiro S. Reduction of endothelial tight junction proteins is related to cerebral aneurysm formation in rats. J Hypertens. 2010;28:1883–91.
Penn DL, Witte SR, Komotar RJ, Sander Connolly E Jr. The role of vascular remodeling and inflammation in the pathogenesis of intracranial aneurysms. J Clin Neurosci. 2014;21:28–32.
Pope FM, Nicholls AC, Narcisi P, Bartlett J, Neil-Dwyer G, Doshi B. Some patients with cerebral aneurysms are deficient in type III collagen. Lancet. 1981;1:973–5.
Jamous MA, Nagahiro S, Kitazato KT, Tamura T, Kuwayama K, Satoh K. Role of estrogen deficiency in the formation and progression of cerebral aneurysms. Part II: experimental study of the effects of hormone replacement therapy in rats. J Neurosurg. 2005;103:1052–7.
Tada Y, Kitazato KT, Tamura T, Yagi K, Shimada K, Kinouchi T, Satomi J. Nagahiro S Role of mineralocorticoid receptor on experimental cerebral aneurysms in rats. Hypertension. 2009;54:552–7.
Stalenhoef AF. The benefit of statins in non-cardiac vascular surgery patients. J Vasc Surg. 2009;49:260–5.
Aoki T, Kataoka H, Ishibashi R, Nozaki K, Hashimoto N. Simvastatin suppresses the progression of experimentally induced cerebral aneurysms in rats. Stroke. 2008;39:1276–85.
Tada Y, Kitazato KT, Yagi K, Shimada K, Matsushita N, Kinouchi T, Kanematsu Y, Satomi J, Kageji T, Nagahiro S. Statins promote the growth of experimentally induced cerebral aneurysms in estrogen-deficient rats. Stroke. 2011;42:2286–93.
Matsushita N, Kitazato KT, Tada Y, Sumiyoshi M, Shimada K, Yagi K, Kanematsu Y, Satomi J, Nagahiro S. Increase in body Na+/water ratio is associated with cerebral aneurysm formation in oophorectomized rats. Hypertension. 2012;60:1309–15.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2016 Springer Japan
About this chapter
Cite this chapter
Nagahiro, S., Kitazato, K. (2016). Experimental Model of Cerebral Aneurysms in Ovariectomized Rats. In: Sata, M. (eds) Mouse Models of Vascular Diseases. Springer, Tokyo. https://doi.org/10.1007/978-4-431-55813-2_13
Download citation
DOI: https://doi.org/10.1007/978-4-431-55813-2_13
Published:
Publisher Name: Springer, Tokyo
Print ISBN: 978-4-431-55811-8
Online ISBN: 978-4-431-55813-2
eBook Packages: MedicineMedicine (R0)