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Involvement of platelet-activating factor in glutamate-induced neurotoxicity

Research Project

Project/Area Number 12671344
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Cerebral neurosurgery
Research InstitutionTOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY

Principal Investigator

HIRASHIMA Yutaka  Toyama Medical and Pharmaceutical University Faculty of Medecine Associate Professor, 医学部, 助教授 (30135016)

Co-Investigator(Kenkyū-buntansha) KURIMOTO Masanori  Toyama Medical and Pharmaceutical University, University Hospital, Assistant Professor, 附属病院, 講師 (10161770)
Project Period (FY) 2000 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2002: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 2001: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 2000: ¥2,200,000 (Direct Cost: ¥2,200,000)
Keywordsplatelet-activating factor / glutamate / PAF acetyl hydrolase / subarachnoid hemorrhage / brain ischemia / chronic subdural hematoma / anti PAF receptor antagonist / 神経細胞 / PAFアセチルハイドロレース / アポトーシス / Etizolam / 再発 / Adenovirus / PAFacetylhydrolase / neuron / apoptosis / anti oxidant / 血小板活性化因子 / アポートシス / 遺伝子導入
Research Abstract

Using an adenoviral vector, we induced overexpression of the plasma type of platelet-activating factor acetylhydrolase (PAFacetylhydrolase) in cultured rat neurons. Neurons overexpressing this enzyme showed a decrease in glutamate-induced injury, mainly, apparent as decreased apoptosis. Reduction of lipid peroxidation by this enzyme and protection of mitochondrial function were demonstrated, and these may be the basis of the resistance to glutamate-induced neuronal injury that we observed.
The efficacy and safety of a new platelet-activating factor receptor antagonist, E5880, were investigated for preventing cerebral vasospasm after subarachnoid hemorrhage (SAH) in 71 patients with SAH who underwent surgery for ruptured aneurysms within 3 days. Intravenous E5880 administration (300μg or 1200μg twice daily) was begun within 4 days and continued for 14 days. The incidence of symptomatic vasospasm, low-density area on computed tomography, and angiographic vasospasm was lower than in placeb … More o groups in previous studies. Clinical outcome was favorable compared with previous studies. No clinically important adverse events were observed. These results suggest that E5880 is safe and effective in the treatment of patients with cerebral vasospasm due to SAH.
Etizolam, an anti-anxiety agent which is an antagonist of platelet-activating factor (PAF) receptors, was administered to patients with chronic subdural hematoma (CSH) after hematoma removal to assess the effectiveness for preventing recurrence compared with control patients not given the drug after surgery. The remaining volumes of subdural hematomas on brain computed tomography were measured approximately 1 month after removal. Volumes in the etizolam group were significantly smaller than those in the control group. Hematoma recurrence was not detected in the etizolam group 3 months after surgery, but was significantly more frequent in the control group. Etizolam administration may be useful for the prevention of recurrence of CSH. Less

Report

(4 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (13 results)

All Other

All Publications (13 results)

  • [Publications] Hirashima Y: "Transfection of the plasma-type platelet-activating factor acetstylhydrolase gene atleruates glutamate-induced apoptosis in cultural rat cortical neurons"Brain Res. 885. 128-132 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hirashima Y: "Effect of a platelet-activating factor receptor antagonist E5880, on cerebral vasospasm after anaouyswel subaraelnoid hemorrylege"Neurol Med Chir (Tokyo). 41. 165-176 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hirashima Y: "Elizolam, an anti-anxiety agent, attenuates recommence of chronic subdural hematome-Evaluation by computed tomography-"Neurol Med Chir (Tokyo). 42. 53-56 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hirashima Y, et al.: "Transfection of the plasma-type platelet-activating factor acetylhydrolase gene attenuates glutamate-indced apoptosis in caltured rat cortical neurous."Brain Res. 885. 128-132 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hirashima Y, et al.: "Eflect of a platelet-activating factor recaptor antagonist, E5880, on cerbral vasospasm after aneurysmal subarachnoid hemorrhage, - Open clinical trial to invesligete efficacy and safety -."Neurol Med Chir (Tokyo). 41. 165-176 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hirashima Y, et al.: "Etigolam, an anti-anxiety agant, athennates recurrence of chronic subdural hematoma - Evaluation by comptued tomo graphy -"Neurol Med Chir (Tokyo). 42. 53-56 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kurimoto M, Hirashima Y, Ogiichi T, Hamada H, Kamiyama H, Endo S: "Establishment and characterization of a novel malignant astrocytoma cell line derived from neurofibromatosis"J Neurosurg. 94. 301-308 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hirashima Y, Endo S, Nakamura S, Kurimoto M, Takaku A: "Cerebral spinal fluid membrane-bound fissue factor and myelin basic protein in the course of vasospasm after subarachnoid hemorrhage"Neurol Res. 23. 715-720 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kamiyama H, Kurimot M, Yamaura J, Uwano T, Hirashima Y, Masahiko K, Endo S, Shiraki K: "Effect of immunity on gene delivery into anterior horn motor neurous by liver attenuated helps simplex virus vector"Gene Ther. 8. 1180-1187 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hirashima Y, Takashima S, Matsumura N, Kurimoto M, Origasa H, Endo S: "Right sylvian fissure subarachnoid hemorrhage has electrocardiographic consequences"Stroke. 32. 2278-2281 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hirashima Y, Kuwayama N, Hamada H, Hayashi N, Endo S: "Etizolam, an anti-auxiety drug, attenuates recurrence of chronic subdural hematoma-Evaluation by computed tomography"Neurol Med Chir(Tokyo). 42. 53-56 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hirashima Y, Endo S, Nukui H, Kobayashi N, Takaku A: "Effect of a platelet-activating factor receptor antagonist, E5880, on cerebral vasospasm after aneurysmal subarachnoid hemorrhege-An open clinical frialto investigate efficacy and safety-"Neurol Med chir(Tokyo). 41. 165-176 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hirashima Y.,Ueno H.,Karasawa K,Yokoyama K,Setaka M.,Takaku A: "Transfection of plasma-type platelet-activating factor a cetyl hydrolase gene attenuates glutamate-induced apoptosis in cultured rat cortical neuroas"Brain Res. 885(1). 128-132 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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