Mechanism of initiation and development of cerebral aneurysm : Using cerebral aneurysm model

• Project/Area Number: 19591705
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Cerebral neurosurgery
• Research Institution: Tokyo Women's Medical University
• Principal Investigator: KASUYA Hidetoshi Tokyo Women's Medical University, 医学部, 教授 (50169455)
• Co-Investigator(Kenkyū-buntansha): YONEYAMA Taku 東京女子医科大学, 医学部, 助教 (90318105) ; INOUE Tatsuya 東京女子医科大学, 医学部, 助教 (70398808) ; AKAGAWA Hiroyuki 東京女子医科大学, 医学部, 助教 (60398807)
• Project Period (FY): 2007 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2009: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2008: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2007: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: cerebral aneurysm / subarachnoid hemorrhage / canine / model / initiation / development / rupture / くも膜下出血 / 脳動脈瘤 / 高血圧 / イヌ / 腎動脈 / 脳動脈 / 脳血管

Research Abstract

The purpose of this study is to establish cerebral aneurysm model in dogs for the study of initiation and development of cerebral aneurysm. Cerebral aneurysms were induced by the treatment of ligation of the common carotid and renal artery, experimental hypertension and β-aminopropionitrile feeding using eleven dogs. Cerebral angiography was performed every three months till 15 months. One animal in the treated group show saccular cerebral aneurysm visualized by cerebral angiography at basilar bifurcation at three months and gradually developed. Histologically, the aneurysm wall was very thin deposited with fibrinoid, internal elastic lamina became thinner and had splits, and number of smooth muscle cells decreased with disturbed arrangement. Thus, this cerebral aneurysm model is similar to that of human. We would like to continue this work for efficiently producing cerebral aneurysm model in large animal.

Research Products

• [Journal Article] Association analysis of genes involved in the maintenance of the integrity of the extracellular matrix with intracranial aneurysms in a Japanese cohort. (2009)
  • Author(s): Ruigrok YM, Rinkel GJ, Wijmenga C, Kasuya H, Tajima A, Takahashi T, Hata A, Inoue I, Krischek B
  • Journal Title: Cerebrovasc Dis 28 Pages: 131-134
• [Journal Article] Cerebral vasospasm following subarachnoid hemorrhage: time for a new world of thought. (2009)
  • Author(s): Pluta RM, Hansen-Schwartz J, Dreier J, Vajkoczy P, Macdonald RL, Nishizawa S, Kasuya H, Wellman G, Keller E, Zauner A, Dorsch N, Clark J, Ono S, Kiris T, Leroux P, Zhang JH
  • Journal Title: Neurol Res 31 Pages: 151-158
• [Journal Article] Gene expression microarray studies of aneurysm walls lead to similar results. (2009)
  • Author(s): Krischek B, Kasuya H
  • Journal Title: Stroke 40
• [Journal Article] Characterization of functional and quality of life in patients following SAH with and without nicardipine prolonged release pellets J (2009)
  • Author(s): Barth M, Thome C, Schmiedek P, Weiss C, Kasuya H, Vajkoczy P
  • Journal Title: Neurosurg 110 Pages: 955-960
• [Journal Article] Follow-up of large aneurysms treated with coil embolization at an acute stage in patients with poor-grade subarachnoid hemorrhage. (2009)
  • Author(s): Hagiwara S, Tanaka N, Tani S, Nakamura S, Ohbuchi H, Hirota K, Iwabuchi S, Kasuya H
  • Journal Title: Interventional Neuroradiology 15 Pages: 45-51
• [Journal Article] Association analysis of genes involved in the maintenance of the integrity of the extracellular matrix with intracranial aneurysms in a Japanese cohort. (2009)
  • Author(s): Ruigrok YM, Rinkel GJ, Wijmenga C, Kasuya H
  • Journal Title: Cerebrovasc Dis 28 Pages: 131-134
  • Peer Reviewed
• [Journal Article] Identification of susceptibility loci for intracranial aneurysm. (2008)
  • Author(s): Bilguvar K, Yasuno K, Niemela M, Ruigrok YM, Fraunberg M, van Duijn CM, van den Berg LH, Mane S, Mason CE, Choi M, Gaal E, Bayri Y, Kolb L, Arlier Z, Ravuri S, Ronkainen A, Tajima A, Laakso A, Hata A, Kasuya H, Breteler MMB, Wijmenga C, State MW, Rinkel GBilguvar K, Yasuno K, Niemela M, Ruigrok YM, Fraunberg M, van Duijn CM, va
  • Journal Title: Nature Genet 40 Pages: 1472-1477
• [Journal Article] Network-based gene expression analysis of intracranial aneurysm tissue reveals role of antigen presenting cells. (2008)
  • Author(s): Krischek B, Kasuya H, Tajima A, Sasaki T, Yoneyama T, Ujiie H, Kubo O, Takakura K, Hori T, Inoue I
  • Journal Title: Neusoscience 154 Pages: 1398-1407
• [Journal Article] Gene-expression in a canine basilar artery vasospasm model: a genome-wide network-based analysis. (2008)
  • Author(s): Sasahara A, Kasuya H, Krischek B, Tajima A, Onda H, Sasaki T, Akagawa H, Hori T, Inoue I
  • Journal Title: Neurosurg Rev 31 Pages: 283-290
• [Journal Article] Gene-expression in a canine basilar artery vasospasm model : a genome-wide network-based analysis (2008)
  • Author(s): Sasahara A, Kasuya H, Krischek B, et al
  • Journal Title: Neurosurg Rev 31 Pages: 283-290
  • Peer Reviewed
• [Journal Article] Network-based gene expression analysis of intracranial aneurysm tissue reveals role of antigen presenting cells (2008)
  • Author(s): Krischek B, Kasuya H, Tajima A, et al
  • Journal Title: Neusoscience 154 Pages: 1398-1407
  • Peer Reviewed
• [Journal Article] Identification of susceptibility loci for intracranial aneurysm Ident ification of susceptibility loci for intracranial aneurysm (2008)
  • Author(s): Bilguvar K, Yasuno K, Niemela M, … Kasuya H, et al
  • Journal Title: Nature Genet 40 Pages: 1472-1477
  • Peer Reviewed
• [Journal Article] Clinical trial of nicardipine prolonged-release implants for preventing vasospasm: Analysis of 100 consecutive patients. (2007)
  • Author(s): Krishcek B, Kasuya H, Onda H, Hori H
  • Journal Title: Neurol Med Chir (Tokyo) 47 Pages: 389-396
• [Journal Article] Systematic screening of lysyl oxidase-like (LOXL) family genes demonstrates that LOXL2 is a susceptible gene to intracranial aneurysms. (2007)
  • Author(s): Akagawa H, Narita A, Yamada H, Tajima A, Krischek B, Kasuya H, Hori T, Kubota M, Saeki N, Hata A, Mizutani T, Inoue I
  • Journal Title: Hum Genet 121 Pages: 377-387
• [Presentation] Development of nicardipine prolongedrelease implants after clipping for preventing cerebral vasospasm. (2010)
  • Author(s): Kasuya H
  • Organizer: Shanghai-Tokyo Neurosurgical Forum
  • Place of Presentation: Shanghai
• [Presentation] Development of nicardipine prolongedrelease implants after clipping for preventing cerebral vasospasm: From laboratory to clinical trial (2010)
  • Author(s): Kasuya H
  • Organizer: 2nd International Conference on Drug Discovery and Therapy
  • Place of Presentation: Dubai
• [Presentation] Clinical trial of nicardipine prolonged-release implants for preventing cerebral vasospasm: Multi-center cooperative study in Tokyo. (2009)
  • Author(s): Kasuya H
  • Organizer: 9th International Conference on Cerebrovascular Surgery
  • Place of Presentation: Nagoya, Japan
• [Presentation] Clinical trial of nicardipine prolonged-release implants for preventing cerebral vasospasm: Multi-center cooperative study in Tokyo. (2009)
  • Author(s): Kasuya H
  • Organizer: 10th International Conference of Cerebral vasospasm
  • Place of Presentation: Chongqing, China
• [Presentation] Molecular genetic analysis of intracranial aneurysm. (2009)
  • Author(s): Kasuya H
  • Organizer: XIV World Congress of Neurological Surgery
  • Place of Presentation: Boston
• [Presentation] Clinical trial of nicardipine prolonged-release implants for preventing vasospasam. (2008)
  • Author(s): Kasuya H, Ohbuchi H, Hagiwara S, Nakamura S, Tani S, Tanaka N
  • Organizer: Russian-Japanese Neurosurgical Symposium
  • Place of Presentation: Saint Petersburg Russia
  • Year and Date: 2008-04-30
• [Book] Macdonald: Neurosurgical Operative Atlas, 2E: Vascular Neurosurgery.(Anterior interhemispheric approach for anterior communicating artery aneurysms.) (2008)
  • Author(s): Kasuya H, Krischek B, Baba M
  • Publisher: Thieme Medical Publishers, Inc.
• [Book] Cerebral vasospasm New strategies in research and treatment Acta Neurochir [Suppl] 104(Kiris T, Zhang JH (eds), Cerebral vasospasm following subarachnoid hemorrhage is completely prevented by L-type calcium channel antagonist in humans.) (2008)
  • Author(s): Kasuya H, Onda H, Krischek B, Hori T
  • Publisher: Springer
• [Book] Cerebral vasospasm New strategies in research and treatment Acta Neurochir [Suppl] 104(Kiris T, Zhang JH (eds), Microarray analysis of hemolysate-induced differential gene expression in cultured human vascular smooth muscle cells (HVSMC).) (2008)
  • Author(s): Sasaki T, Kasuya H, Aihara Y, Hori T
  • Publisher: Springer