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Rat Model of Intracranial Aneurysm: Variations, Usefulness, and Limitations of the Hashimoto Model

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Subarachnoid Hemorrhage

Part of the book series: Acta Neurochirurgica Supplement ((NEUROCHIRURGICA,volume 127))

Abstract

Given the poor outcome of subarachnoid hemorrhage due to rupture of intracranial aneurysms (IAs) and high prevalence of IAs in general public, elucidation of mechanisms underlying the pathogenesis of the disease and development of effective treatment are mandatory for social health. Recent experimental findings have revealed the crucial contribution of macrophage-mediated chronic inflammation to and greatly promoted our understanding of the pathogenesis. Also a series of studies have proposed the potential of anti-inflammatory drugs as therapeutic ones. In this process, a rodent model of IAs plays an indispensable role. Basic concept of IA induction in such kind of models is that IA formation is triggered by hemodynamic stress loaded on damaged arterial walls. To be more precise, although detailed procedures are different among researchers, animals are subjected to a ligation of a unilateral carotid artery and systemic hypertension achieved by a salt overloading, and IAs are induced at the contralateral bifurcation site. Importantly, trigger of IA formation in the model mimics human one, and IA lesions induced share similarity in histology with human ones such as degenerative changes of media. For further elucidating the pathogenesis, we need to well understand variations, usefulness, and also limits of this model.

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References

  1. Aoki T, Frosen J, Fukuda M, Bando K, Shioi G, Tsuji K, Ollikainen E, Nozaki K, Laakkonen J, Narumiya S. Prostaglandin E2-EP2-NF-kappaB signaling in macrophages as a potential therapeutic target for intracranial aneurysms. Sci Signal. 2017;10.

    Google Scholar 

  2. Aoki T, Nishimura M. Targeting chronic inflammation in cerebral aneurysms: focusing on NF-kappaB as a putative target of medical therapy. Expert Opin Ther Targets. 2010;14:265–73.

    Article  CAS  Google Scholar 

  3. Aoki T, Nishimura M. The development and the use of experimental animal models to study the underlying mechanisms of CA formation. J Biomed Biotechnol. 2011;2011:535921.

    Article  Google Scholar 

  4. Aoki T, Nozaki K. Preemptive medicine for cerebral aneurysms. Neurol Med Chir. 2016;56:552–68.

    Article  Google Scholar 

  5. Cai J, He C, Yuan F, Chen L, Ling F. A novel haemodynamic cerebral aneurysm model of rats with normal blood pressure. J Clin Neurosci. 2012;19:135–8.

    Article  Google Scholar 

  6. Fukuda M, Aoki T. Molecular basis for intracranial aneurysm formation. Acta Neurochir Suppl. 2015;120:13–5.

    PubMed  Google Scholar 

  7. Greving JP, Wermer MJ, Brown RD Jr, Morita A, Juvela S, Yonekura M, Ishibashi T, Torner JC, Nakayama T, Rinkel GJ, Algra A. Development of the PHASES score for prediction of risk of rupture of intracranial aneurysms: a pooled analysis of six prospective cohort studies. Lancet Neurol. 2014;13:59–66.

    Article  Google Scholar 

  8. Hashimoto N, Handa H, Hazama F. Experimentally induced cerebral aneurysms in rats. Surg Neurol. 1978;10:3–8.

    CAS  PubMed  Google Scholar 

  9. Hashimoto N, Kim C, Kikuchi H, Kojima M, Kang Y, Hazama F. Experimental induction of cerebral aneurysms in monkeys. J Neurosurg. 1987;67:903–5.

    Article  CAS  Google Scholar 

  10. 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.

    Article  CAS  Google Scholar 

  11. Miyamoto T, Kung DK, Kitazato KT, Yagi K, Shimada K, Tada Y, Korai M, Kurashiki Y, Kinouchi T, Kanematsu Y, Satomi J, Hashimoto T, Nagahiro S. Site-specific elevation of interleukin-1beta and matrix metalloproteinase-9 in the Willis circle by hemodynamic changes is associated with rupture in a novel rat cerebral aneurysm model. J Cereb Blood Flow Metab. 2017;37:2795–805.

    Article  CAS  Google Scholar 

  12. 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.

    Article  Google Scholar 

  13. Nagata I, Handa H, Hashimoto N, Hazama F. Experimentally induced cerebral aneurysms in rats: part VI. Hypertension. Surg Neurol. 1980;14:477–9.

    CAS  PubMed  Google Scholar 

  14. Narayanan AS, Siegel RC, Martin GR. On the inhibition of lysyl oxidase by-aminopropionitrile. Biochem Biophys Res Commun. 1972;46:745–51.

    Article  CAS  Google Scholar 

  15. Rinkel GJ, Djibuti M, Algra A, van Gijn J. Prevalence and risk of rupture of intracranial aneurysms: a systematic review. Stroke. 1998;29:251–6.

    Article  CAS  Google Scholar 

  16. Turjman AS, Turjman F, Edelman ER. Role of fluid dynamics and inflammation in intracranial aneurysm formation. Circulation. 2014;129:373–82.

    Article  Google Scholar 

  17. Wermer MJ, van der Schaaf IC, Algra A, Rinkel GJ. Risk of rupture of unruptured intracranial aneurysms in relation to patient and aneurysm characteristics: an updated meta-analysis. Stroke. 2007;38:1404–10.

    Article  Google Scholar 

  18. Yamamoto R, Aoki T, Koseki H, Fukuda M, Hirose J, Tsuji K, Takizawa K, Nakamura S, Miyata H, Hamakawa N, Kasuya H, Nozaki K, Hirayama Y, Aramori I, Narumiya S. A sphingosine-1-phosphate receptor type 1 agonist, ASP4058, suppresses intracranial aneurysm through promoting endothelial integrity and blocking macrophage transmigration. Br J Pharmacol. 2017;174:2085–101.

    Article  CAS  Google Scholar 

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Acknowledgment

The authors express their sincere gratitude to all the researchers, assistants, secretaries, and grants supporting their research works.

Conflict of Interest: The authors declare that they have no conflict of interest.

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Correspondence to Tomohiro Aoki .

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Aoki, T., Miyata, H., Abekura, Y., Koseki, H., Shimizu, K. (2020). Rat Model of Intracranial Aneurysm: Variations, Usefulness, and Limitations of the Hashimoto Model. In: Martin, R., Boling, W., Chen, G., Zhang, J. (eds) Subarachnoid Hemorrhage. Acta Neurochirurgica Supplement, vol 127. Springer, Cham. https://doi.org/10.1007/978-3-030-04615-6_6

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  • DOI: https://doi.org/10.1007/978-3-030-04615-6_6

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