Research for producing the rapeutic agents on proteinkinase C to inhibit cerebral vasospasm following subarachnoid hemorrhage

• Project/Area Number: 20591699
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Cerebral neurosurgery
• Research Institution: University of Occupational and Environmental Health, Japan
• Principal Investigator: NISHIZAWA Shigeru 産業医科大学, 医学部, 教授 (40135257)
• Co-Investigator(Renkei-kenkyūsha): AKIBA Daisuke 産業医科大学, 医学部, 助教 (20441834) ; AOYAMA Yuichi 産業医科大学, 医学部, 助教 (50373155)
• Project Period (FY): 2008 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2012: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2011: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2010: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2009: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2008: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: クモ膜下出血 / 脳血管攣縮 / 蛋白リン酸化酵素C / アイソフォーム / 創薬 / 淡白リン酸化酵素C / アイソフオーム

Research Abstract

Cerebral vasospasm following subarachnoidhemorrhage(SAH)is an important factor to improve prognosis of the SAH patients. The mechanisms of cerebral vasospasm has still been unknown. PKCa and PKCd are most important candidates to produce cerebral vasospasm according to our own research results. The aim of this research is to search an inhibitor on both PKC isoforms and to produce therapeutic agents for inhibition of cerebral vasospasm. An inhibitor was found through the research, but production of therapeutic agent has no been available. Insertion of a catheter into subarachnoid space and continuous administration of the drug is considered to be a realistic way so far.

Research Products

• [Journal Article] The role of early brain injury in cerebral vasospasm following subarachnoid hemorrhage: From clinical and scientific aspects (2013)
  • Author(s): Nishizawa S
  • Journal Title: Acta Neurochir Volume: 115(suppl) Pages: 207-212
  • DOI: 10.1007/978-3-7091-1192-5_38
  • ISBN: 9783709111918, 9783709111925
  • Peer Reviewed
• [Journal Article] Roles of signal transduction mechanisms in cerebral vasospasm following subarachnoid hemorrhage : Overview (2012)
  • Author(s): Nishizawa S
  • Journal Title: Acta Neurochirurgica Supplement Volume: 110 Pages: 27-30
  • Peer Reviewed
• [Journal Article] Roles of signal transduciton mechanisms in cerebral vasospasm following subarahnoid hemorrhage: Overview (2011)
  • Author(s): Nishizawa S
  • Journal Title: Acta Neurochir Volume: 110(suppl) Pages: 27-34
  • DOI: 10.1007/978-3-7091-0353-1_5
  • ISBN: 9783709103524, 9783709103531
  • Peer Reviewed
• [Journal Article] Roles of signal tranduction mechanisms in cerebral vasospasm following subarachnoid hemorrhage. (2011)
  • Author(s): Nishizawa, S
  • Journal Title: Acta Neurocirurgica Supplementum Supplement 110 Pages: 27-34
  • Peer Reviewed
• [Journal Article] Roles of signal tranduction mechanisms in cerebral vasospasm following subarachnoid hemorrhage : Overview (2011)
  • Author(s): Nishizawa S
  • Journal Title: Acta Neurocirurgica Supplementum Supplement Volume: 110 Pages: 27-34
  • Peer Reviewed
• [Journal Article] Role of interleukin-1 (beta) in early brain injury after subarachnoid hemorrhage in mice. (2009)
  • Author(s): Nishizawa, S
  • Journal Title: Stroke 40 Pages: 2519-2525
  • Peer Reviewed
• [Journal Article] Multifaceted effects of selective inhibitor of phosphodiesterase III, Cilostazole, for cerebral vasospasm after subarachnoid hemorrhage in a dog model. (2009)
  • Author(s): Nishizawa, S
  • Journal Title: Cerebrovascular Diseases 28 Pages: 135-142
  • Peer Reviewed
• [Journal Article] Cerebral vasospasm following subarachnoid hemorrhage : time for a new world of thought. (2009)
  • Author(s): Nishizawa, S
  • Journal Title: Neurological Research 31 Pages: 151-158
  • Peer Reviewed
• [Journal Article] Role of interleukin-1 (beta) in early brain injury after subarachnoid hemorrhage in mice. (2009)
  • Author(s): Nishizawa S
  • Journal Title: Stroke 40 Pages: 2519-2525
  • Peer Reviewed
• [Journal Article] Multifaceted effects of selective inhibitor of phosphodiesterase III, Cilostazole, for cerebral vasospasm after subarachnoid hemorrhage in a dog model. (2009)
  • Author(s): Nishizawa S
  • Journal Title: Cerebrovascular Diseases 28 Pages: 135-142
  • Peer Reviewed
• [Journal Article] Cerebral vasospasm following subarachnoid hemorrhage : time for a new world of thought. (2009)
  • Author(s): Nishizawa S
  • Journal Title: Neurological Research 31 Pages: 151-158
  • Peer Reviewed
• [Journal Article] The roles of cross-talk mechanisms in the signal transduction system in the pathophysiology of the cerebral vasospasm after subarachnoid hemorrhage. what we know and what do not know. (2008)
  • Author(s): Nishizawa, S
  • Journal Title: Acta Neurochir suppl(Wien) 104 Pages: 59-63
  • Peer Reviewed
• [Journal Article] The roles of cross-talk mechanisms in the signal transduction systems in the pathophysiology of the cerebral vasospasm after aubarachnoid haemorrhge-what we know and what we do not know. (2008)
  • Author(s): Nishizawa S
  • Journal Title: Acta Neurochir Suppl (Wien) 104 Pages: 59-63
  • Peer Reviewed
• [Journal Article] くも膜下出血後の脳血管攣縮-基礎研究と治療における現在と将来の展望 (2008)
  • Author(s): 西澤茂
  • Journal Title: 脳神経外科 36 Pages: 121-133
  • Peer Reviewed
• [Journal Article] くも膜下出血後の脳血管攣基礎研究における現在と今後の展望 (2008)
  • Author(s): 西澤茂
  • Journal Title: 脳血管攣縮 24 Pages: 20-23
  • Peer Reviewed
• [Presentation] くも膜下出血後の急性期ノン損傷における活性型ミクログリアの役割 (2013)
  • Author(s): 西澤 茂
  • Organizer: STROKE 2013
  • Place of Presentation: 新高輪プリンスホテル（東京）
• [Presentation] Imaging of early brain injury following subarachnoid hemorrhage (2013)
  • Author(s): Shigeru Nishizawa
  • Organizer: Vasosaspm 2013
  • Place of Presentation: Lucerne, Switzerland
• [Presentation] Role of brain injury following subarachnoid hemorrhage (2011)
  • Author(s): Nishizawa S
  • Organizer: Vasospasm 2011
  • Place of Presentation: Hilton Cincinnati Netherland Plaza, Cincinnati, Ohio, USA(招待講演)
  • Year and Date: 2011-07-22
• [Presentation] The roles of signal transduction systems in pathophysiological mechanisnls of cerebral vasospasm - Overview- (2011)
  • Author(s): Nishizawa S
  • Organizer: 11th International Conference of Cerebral Vasospasm (Vasospasnl 2011)
  • Place of Presentation: Cincinnati, Ohio, USA
• [Presentation] クモ膜下出血後の血管攣縮に対する治療戦略 (2010)
  • Author(s): 西澤茂
  • Organizer: 東京脳血管フオーラム
  • Place of Presentation: 東京
  • Year and Date: 2010-08-26
• [Presentation] クモ膜下出血後の血管攣縮に対する治療戦略 (2010)
  • Author(s): 西澤茂
  • Organizer: 東京脳血管フォーラム
  • Place of Presentation: ヒルトン東京(東京)(講演)
  • Year and Date: 2010-08-26
• [Presentation] Signal transduction in cerebral vasospasm following subarachnoid hemorrhage. (2009)
  • Author(s): 西澤茂
  • Organizer: The 10th international conference on cerebral vasospasm
  • Place of Presentation: CHINA
  • Year and Date: 2009-10-09
• [Presentation] Signal transduction in cerebral vasospasm following subarachnoid hemorrhage-Overview (2009)
  • Author(s): Nishizawa S
  • Organizer: 第10回国際脳血管攣縮学会
  • Place of Presentation: 重慶 中華人民共和国
  • Year and Date: 2009-10-08
• [Presentation] 脳血管攣縮と形質転換-シロスタゾールの薬理効果 (2009)
  • Author(s): 西澤茂
  • Organizer: スパズムシンポジウム
  • Place of Presentation: 松江
  • Year and Date: 2009-03-20
• [Presentation] 脳血管攣と形質転換-シロスタゾールの薬理効果 (2009)
  • Author(s): 西澤茂
  • Organizer: スパスムシンポジウム
  • Place of Presentation: 松江
  • Year and Date: 2009-03-20
• [Presentation] Vasospasm Biochemistry (2009)
  • Author(s): Nishizawa S
  • Organizer: 10th International Conference of Cerebral Vasospasm
  • Place of Presentation: Isutanbul Turkey
• [Presentation] Treatment of vasospasm.-Scientific viewpoints to clinical use- (2009)
  • Author(s): Nishizawa S
  • Organizer: 10th International Conference of Cerebral Vasospasm
  • Place of Presentation: Isutanbul Turkey
• [Book] Biochemical assessment of cerebral vasospasm: Measurement of cGMP, PKC, and PTR in cerebral arteries (2012)
  • Author(s): Koide M, Nishizawa S
  • Publisher: Part VII Cerebral Vasospasm, in Animal Models of Acute Neurological Injuries II, (Edt:Chen J, Xu XM, Xu ZC, and Zhang J), Humana Press, USA
• [Book] Animal Models of Acute Neurological Injuries (2008)
  • Author(s): Nishizawa, S
  • Publisher: The Human Press Inc
• [Book] Animal Models of Acute Neurological Injuries (2008)
  • Author(s): Nishizawa S
  • Publisher: The Human Press Inc. Totowa, USA