Development of new treatments to prevent rupture of intracranial aneurysms

• Project/Area Number: 25861279
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurosurgery
• Research Institution: The University of Tokushima
• Principal Investigator: TADA YOSHITERU 徳島大学, ヘルスバイオサイエンス研究部, 助教 (30547964)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 脳動脈瘤破裂 / エストロゲン / くも膜下出血 / 脳・神経、脳神経疾患 / 脳・神経 / 脳神経疾患

Outline of Final Research Achievements

The aim of this study was to establish pharmacological treatments for prevention of rupture of intracranial aneurysms. To test pharmacological therapy, we established a rat model of intracranial aneurysms in which spontaneous aneurysm rupture occurred. Female rats were subjected to estrogen deficiency, hemodynamic stress, and renal hypertension. In this model, we demonstrated that endothelial dysfunction, oxidative stress, inflammation, and high salt intake were associated with the formation of intracranial aneurysms. Various types of drugs prevent the formation of intracranial aneurysms. Furthermore, to examine the mechanisms of aneurysmal rupture, we modified this model. In modified model, rats had a higher incidence of aneurysmal rupture. In the future study, we will examine the mechanisms of aneurysmal rupture and test the pharmacological therapy for prevention of aneurysmal rupture.

Research Products

• [Journal Article] Angiotensin-(1-7) protects against the development of aneurysmal subarachnoid hemorrhage in mice (2015)
  • Author(s): Shimada K, Furukawa H, Wada K, Wei Y, Tada Y, Kuwabara A, Shikata F, Kanematsu Y, Lawton MT, Kitazato KT, Nagahiro S, Hashimoto T
  • Journal Title: J Cereb Blood Flow Metab Volume: in press Issue: 3 Pages: 191-196
  • DOI: 10.1159/000365653
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Roles of estrogen in the formation of inctracranial aneurysms in ovariectomized female mice (2014)
  • Author(s): Tada Y, Makino H, Furukawa H, Shimada K, Wada K, Liang EI, Murakami S, Kudo M, Kung DK, Hasan DM, Kitazato KT, Nagahiro S, Lawton MT, Hashimoto T
  • Journal Title: Neurosurgery Volume: 75 Issue: 6 Pages: 690-695
  • DOI: 10.1227/neu.0000000000000528
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Roles of hypertension in the rupture of intracranial aneurysms (2014)
  • Author(s): Tada Y, Wada K, Shimada K, Makino H, Liang EI, Murakami S, Kudo M, Kitazato KT, Nagahiro S, Hashimoto T
  • Journal Title: Stroke Volume: 45 Issue: 2 Pages: 579-586
  • DOI: 10.1161/strokeaha.113.003072
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Estrogen protects against intracranial aneurysm rupture in ovariectomized mice (2014)
  • Author(s): Tada Y, Wada K, Shimada K, Makino H, Liang EI, Murakami S, Kudo M, Shikata F, Silva RAP, Kitazato KT, Hasan DM, Kanematsu Y, Nagahiro S, Hashimoto T
  • Journal Title: Hypertension Volume: 63 Issue: 6 Pages: 1339-1344
  • DOI: 10.1161/hypertensionaha.114.03300
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Estrogen protects against intracranial aneurysm rupture in ovariectomized mice. (2014)
  • Author(s): Tada Y, Wada K, Shimada K, Makino H, Liang EI, Murakami S, Kudo M, Shikata F, Pena Silva RA, Kitazato KT, Hasan DM, Kanematsu Y, Nagahiro S, Hashimoto T
  • Journal Title: Hypertension Volume: in press
  • Peer Reviewed
• [Journal Article] 脳動脈瘤におけるNa+蓄積とRASの影響. (2013)
  • Author(s): 多田恵曜, 北里慶子, 永廣信治
  • Journal Title: Angiotensin Research Volume: 10 Pages: 20-28
• [Presentation] Predominant activation of M2 macrophage by Group-specific component protein-derived macrophage activating factor in the late phase of cerebral ischemia may contribute to neurogenesis (2015)
  • Author(s): Kurashiki Y, Kitazato KT, Shimada K, Yaji K, Tada Y, Sumiyoshi M, Takeshi M, Satomi J, Kageji T, Nagahiro S
  • Organizer: International stroke conference
  • Place of Presentation: Nashville, USA
  • Year and Date: 2015-02-11 – 2015-02-13
• [Presentation] Hemodynamic changes may be partly attributable to the formation and rupture of aneurysms in a rat model. (2015)
  • Author(s): Miyamoto T, Kohrai M, Kung D, Kitazato KT, Shimada K, Yaji K, Tada Y, Kurashiki Y, Kuwayama K, Satomi J, Nagahiro S
  • Organizer: International stroke conference
  • Place of Presentation: Nashville, USA
  • Year and Date: 2015-02-11 – 2015-02-13
• [Presentation] Protective effects of estrogen receptor-beta against the formation of intracranial aneurysms in mice (2014)
  • Author(s): Tada Y, Makino H, Wada K, Shimada K, Liang EI, Murakami S, Kudo M, Kitazato KT, Nagahiro S, Hashimoto T
  • Organizer: World stroke congress
  • Place of Presentation: Istanbul, Turkey
  • Year and Date: 2014-10-22 – 2014-10-25
• [Presentation] Role of angiotensin (1-7) and angiotensin type 2 receptor on intracranial aneurysmal rupture. (2014)
  • Author(s): Shimada K, Wada K, Tada Y, Wei Y, Kuwabara A, Shikata F, Furukawa H, Kitazato KT, Nagahiro S, Hashimoto T
  • Organizer: International stroke conference 2014.
  • Place of Presentation: San Diego Convention Center, San Diego, USA