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Neuroprotective effects of synthetic pyrimidine compound in focal cerebral ischemia

Research Project

Project/Area Number 14571337
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Cerebral neurosurgery
Research InstitutionTokyo Women's Medical University

Principal Investigator

KAWAMATA Takakazu  Tokyo Women's Medical University, School of Medicine, Instructor, 医学部, 助手 (90204768)

Co-Investigator(Kenkyū-buntansha) HORI Tomokatsu  Tokyo Women's Medical University, School of Medicine, Professor, 医学部, 教授 (60010443)
YAMANE Fumitaka  Tokyo Women's Medical University, School of Medicine, Instructor, 医学部, 助手 (60210506)
NAKAJIMA Hiroshi  Tokyo Women's Medical University, School of Medicine, Instructor, 医学部, 助手 (80227800)
NAKAMURA Satoshi  Tokyo Women's Medical University, School of Medicine, Instructor, 医学部, 助手 (20266779)
MITSUYAMA Tetsuryu  Tokyo Women's Medical University, School of Medicine, Instructor, 医学部, 助手 (80318104)
Project Period (FY) 2002 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2003: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2002: ¥1,600,000 (Direct Cost: ¥1,600,000)
KeywordsCerebral ischemia / Cerebral infarction / Pyrimidine compound / MS-818 / Neurological dysfunction / Stroke
Research Abstract

MS-818(2-piperadino-6-methyl-5-oxo-5,6-dihydro-(7H) pyrrolo-[3,4-d] pyrimidine maleate) is a synthetic heterocyclic pyrimidine compound reported to have a variety of biological activities including neurite outgrowth, astrocyte differentiation, suppression of neuronal apoptosis, regeneration of injured peripheral nerves, fracture repairs, angiogenesis and superovulation. Aiming to exploit the neurotrophic effects of MS-818, we evaluated the effect of the synthetic pyrimidine derivative on infarct volume reduction and amelioration of sensorimotor dysfunction in a rat model of focal ischemia.
Male Sprague-Dawley rats were subjected to right middle cerebral artery occlusion. MS-818(1,5,or 10 mg/kg) or phosphate buffered saline (control group)(totally 4 groups ; n=10 in each group) was administered intraperitoneally at the time of ischemic onset and 24 hours later. Rats were killed at 48 hours after the stroke surgery, and infarct volume was determined by an image analysis program following staining with 2,3,5-triphenyltetrazolium chloride. Postischemic neurological deficit and body weight were also assessed.
Significant infarct volume reductions (total and cortical infarction) were found in the all the MS-818 groups compared with the control group. Furthermore, MS-818 induced significant amelioration of sensorimotor function in forelimb and hindlimb placing tests. The present findings suggest that MS-818,which has a much smaller molecular weight than neurotrophic peptides, represent a new approach to the treatment of focal cerebral ischemia.

Report

(4 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (6 results)

All 2004 2003 2002

All Journal Article (6 results)

  • [Journal Article] Pravastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, reduces delayed neuronal death following transient forebrain ischemia in the adult rat hippocampus.2004

    • Author(s)
      Daimon M, Aomi S, Kawamata T, Kurosawa H
    • Journal Title

      Neuroscience Letter 362

      Pages: 122-126

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Pravastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, reduces delayed neuronal death following transient forebrain ischemia in the adult rat hippocampus.2004

    • Author(s)
      Daimon M, Aomi S, Kawamata T, Kurosawa H
    • Journal Title

      Neurosci Lett 362

      Pages: 122-126

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Divergence in signaling pathways involved in promotion of cell viability mediated by bFGF, NGF, and EGF in PC12 cells2003

    • Author(s)
      Kawamata T, Yamaguchi T, Shin-ya K, Hori T
    • Journal Title

      Neurochemical Research 28

      Pages: 1221-1225

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Divergence in signaling pathways involved in promotion of cell viability mediated by bFGF, NGF, and EGF in PC12 cells.2003

    • Author(s)
      Kawamata T, Yamaguchi T, Shin-ya K, Hori T
    • Journal Title

      Neurochem Res 28

      Pages: 1221-1225

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] A synthetic pyrimidine compound MS-818 reduces infarct size and ameliorates sensorimotor dysfunction following permanent focal cerebral ischemia in rats.2002

    • Author(s)
      Mitsuyama T, Kawamata T, Yamane Y, Awaya A, Hori T
    • Journal Title

      Journal of Neurosurgery 96

      Pages: 1072-1076

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] A synthetic pyrimidine compound MS-818 reduces infarct size and ameliorates sensorimotor dysfunction following permanent focal cerebral ischemia in rats.2002

    • Author(s)
      Mitsuyama T, Kawamata T, Yamane Y, Awaya A, Hori T
    • Journal Title

      J Neurosurg 96

      Pages: 1072-1076

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary

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Published: 2002-04-01   Modified: 2016-04-21  

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