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Pharmacological investigation for mechanisms of cerebral hemorrhage induced by anti-thrombotic agents

Research Project

Project/Area Number 15390173
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Applied pharmacology
Research InstitutionHamamatsu University School of Medicine

Principal Investigator

UMEMURA Kazuo  Hamamatsu University School of Medicine, Professor, 医学部, 教授 (40232912)

Co-Investigator(Kenkyū-buntansha) SUZUKI Yasuhiro  Hamamatsu University School or Medicine, Assistant Professor, 医学部, 助手 (00324343)
池田 康彦  浜松医科大学, 医学部, 助手 (50293618)
Project Period (FY) 2003 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥9,900,000 (Direct Cost: ¥9,900,000)
Fiscal Year 2005: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2004: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2003: ¥3,500,000 (Direct Cost: ¥3,500,000)
Keywordsstroke / cerebral hemorrhage / heparin / tPA / MMP-9
Research Abstract

Cerebral hemorrhage associated with antithrombotic and thrombolytic therapy in acute stroke is a major clinical problem. We investigated the roles of endogenous tPA and MMPs in hemorrhagic cerebral infarction associated with heparin. We demonstrated that heparin administration caused cerebral hemorrhage in WT but not in KO. Heparin administration increased tPA activity and its mRNA expression in WT. We also observed an induction of MMP9 and its mRNA expression by heparin administration in WT but not in KO. Our findings suggest that endogenous tPA plays an important role in heparin-produced cerebral hemorrhage via MMP9 induction and activation.

Report

(4 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • Research Products

    (11 results)

All 2005 2004 Other

All Journal Article (6 results) Publications (5 results)

  • [Journal Article] Positron Emission Tomographic Study of the Neuroprotective Effect of TRA-418, an Anti-Platelet Agent, in a Monkey Model of Stroke.2005

    • Author(s)
      Umemura, K., Tsukada, H., Kakiuchi, T., Yamada, N., Matsuura, N.
    • Journal Title

      J Nucl Med 46

      Pages: 1931-1936

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Neuroprotective effects of KCL-440, a new poly(ADP-ribose)polymerase inhibitor, in the rat middle cerebral artery occlusion model.2005

    • Author(s)
      Ikeda, Y., Hokamura, K., Kawai, T., Ishiyama, J., Ishikawa, K., Anraku, T., Uno, T., Umemura, K.
    • Journal Title

      Brain Res 1060

      Pages: 73-80

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Experimental study on the pro tective effects of edaravone against ischemic spinal cord injury.J2005

    • Author(s)
      Suzuki, K., Kazui, T., Terada, H., Umemura, K., Ikeda, Y., Bashar, A.H.M., Yamashita, K., Washiyama, N., Suzuki, T., Ohkura, K., Yasuike, J.
    • Journal Title

      Thorac Cardiov Sur 130

      Pages: 1586-1592

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Essential role of endogenous tissue plasminogen activator via matrix metallop roteinase 9 induction and expression on heparin-produced cerebral hemorrhage after cerebral ischemia in mice.2004

    • Author(s)
      Zhao B.Q., Ikeda Y., Ihara H., Urano T., Fan W.Y., Mikawa S., Suzuki Y., Kondo K., Sato K., Nagai N., Umemura K.
    • Journal Title

      Blood 103

      Pages: 2610-2616

    • Related Report
      2004 Annual Research Report
  • [Journal Article] A Na^+/H^+ exchanger inhibitor, SM-20220, is protective against excitotoxicity in cultured cortical neurons.2004

    • Author(s)
      Matsumoto Y., Yamamoto S., MD, Suzuki Y., Tsuboi, T., Terakawa S.Ohashi N., Umemura K.
    • Journal Title

      Stroke 35

      Pages: 185-190

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Neuroprotective effects of ONO-1924H, an inhibitor of poly ADP-ribose polymerase (PARP), on cytotoxicity of PC12 cells and ischemic cerebral damage.2004

    • Author(s)
      Kamanaka Y., Kondo K., Ikeda Y., Kamoshimo W., Kitajima T., Suzuki Y., Nakamura Y., Umemura K
    • Journal Title

      Life Sciences 76

      Pages: 151-162

    • Related Report
      2004 Annual Research Report
  • [Publications] Suzuki Y., Takagi Y., Nakamura R., Hashimoto K., Umemura K.: "Ability of NMDA and non-NMDA receptor antagonists to inhibit cerebral ischemic damage in aged rats."Brain Res. 964. 116-120 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yamada N., Miyamoto M., Isogaya M., Suzuki M., Ikezawa S., Hoshi K., Ohno M., Takeda T., Otake A., Umemura K.: "TRA-418, a novel compound having both thromboxane A_2 receptor antagonistic and prostaglandin I_2 receptor agonistic activities : its antiplatelet effects in human and animal platelets."J Thromb Haemostasis. 1. 1813-1819 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Katsuta K., Umemura K., Ueyama N., Matsuoka N.: "Pharmacological evidence for a correlation between hippocampal CA1 cell damage and hyperlocomotion following global cerebral ischemia in gerbils."Eur J Pharmacol. 467. 103-109 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Miyamoto M., Yamada N., Ikezawa S., Ohno M., Otake A., Umemura K., Matsushita T.: "Effects of TRA-418, a novel TP-receptor antagonist, and IP-receptor agonist, on human platelet activation and aggregation."Bri J Pharmacol. 140. 889-894 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yamamoto S., Matsumoto Y., Suzuki Y., Tsuboi T., Terakawa S., Ohashi N., Umemura K.: "An Na+/H+ exchanger inhibitor suppresses cellular swelling and neuronal death induced by glutamate in cultured cortical neurons."Acta Neurochir Suppl.. 86. 223-226 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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