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The protective effects of sphingolipid synthetic drug (L-PDMP) on apoptotic cell damage in cerebral infarction

Research Project

Project/Area Number 11557108
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Cerebral neurosurgery
Research InstitutionTeikyo Univ. School of Med.

Principal Investigator

NAKAGONI Tadayoshi  Teikyo Univ., School of Medicine, Professor, 医学部, 教授 (90198052)

Co-Investigator(Kenkyū-buntansha) NAKANE Makoto  Teikyo Univ., School of Medicine, Assistant, 医学部, 助手 (00266305)
KUBOTA Masaru  Teikyo Univ., School of Medicine, Associate Professor, 医学部, 助教授 (30246061)
TAMURA Akira  Teikyo Univ., School of Med., Professor, 医学部, 教授 (80111532)
MASUDA Hiroyuki  Seikagaku Co. Ltd., Research Fellow, 生物研究室・主任研究員
INOGUCHI Jinichi  Hokkaido Univ., Graduate School of Pharm., Associate Prof., 大学院・薬学研究科, 助教授 (70131810)
成田 孝而  帝京大学, 医学部, 助手 (90237602)
金光 秀晃  帝京大学, 医学部, 講師 (10129992)
Project Period (FY) 1999 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥13,400,000 (Direct Cost: ¥13,400,000)
Fiscal Year 2001: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2000: ¥5,700,000 (Direct Cost: ¥5,700,000)
Fiscal Year 1999: ¥5,000,000 (Direct Cost: ¥5,000,000)
KeywordsSphingolipid / Focal ischemia / L-PDMP / Behavior / MCA / Glucosylceramide / Sphingomyelin / hypothermia / delay neuronal death / ganglioside / 中大脳動脈閉塞モデル / グルコシルセラミド / 水迷路 / セラミド / スフィンゴミエリン / ceramide / D-PDMP
Research Abstract

L-PDMP (L-threo-l-phenyl-2-decanoylamino-3-morpholino-l-propanol) exhibits stimulatory effects on glycosphingolipid biosynthesis and its neurotrophic actions in cultured neuron. The effects of intraperitoneal administration of L-PDMP on sphingolipid metabolism and behavioral changes in the rat following permanent occlusion of the left middle cerebral artery (MCA) were investigated. The L-PDMP treatment induced increases in glucosylceramide (ganglioside precursor) and sphingomyelin (SM) levels in the ischemic cerebral cortex, and improved acquisition of memory and learning in the Morris water maze task. The pharmacological effects of L-PDMP have been proposed to have a significant activity on promoting cell survival and improving neural functions.

Report

(4 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • Research Products

    (25 results)

All Other

All Publications (25 results)

  • [Publications] Kubota, M.Nakane, T.Nakagomi, A.Tamura, H.Hisaki, H.Shimasaki: "Regional distribution of ethanolamine plasmalogen in the hippocampal CA1 and CA3 regions and cerebral cortex of the gerbil"Neuroscience Letters. 301. 175-178 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nakane M, Kubota M, Nakagomi T, Tamura A, et al.: "Rewarming eliminates the protective effect of cooling against delayed neuronal death"Neuro Report. 12. 2439-2442 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 田村 晃, 久保田 勝, 成田考而, 中山比登志: "脳虚血の病態生理"集中治療. 12巻、7号. 705-712 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kubota, M.Nakane, T.Nakagomi, A.Tamura, H, Hisaki, H.Shimasaki: "Sphingolipid biosynthesis by L-PDMP after rat MCA occlusion"Acta Neurochir. 76. 339-341 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nakane M, Tamjura A, Miyasaka N, Nagaoka T, Kuroiwa T: "Astrocytic swelling in the ipsilateral substantia nigra after occlusion of the middle cerebral artery in rats"AJNR Am J Neuroradiol. 22. 660-663 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kubota M, Nakane M, Nakagomi T, Tamura A., et al.: "Mild hypothermia reduces the rate of metabolism of arachidonic acid following postischemic reperfusion"Brain Res. 779. 297-300 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kubota M., Nakane M., Nakagomi T., Tamura A., et al.: "Regional distribution of ethanolamine plasmalogen in the hippocampal CA1 and CA3 regions and cerebral cortex of the gerbil"Meuroscience Letter. 301. 175-178 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Zhao F., Kuroiwa T., Miyasaka N., Tamura A., et al.: "Characteristic changes in T2-value, apparent diffusion coefficient, and ultrastructure of substantia nigra evolving exofocal postischemic neuronal death in rats"Brain Res.. 895. 238-214 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nakane M., Kubota M., Nakagomi T., Tamura A., et al.: "Rewarming eliminates the protective effect of cooling again : delayed neuronal death"NeuroReport. 12. 2439-2442 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nakane M., Tamura A., Miyasaka N., Nagaoka T., Kuroiwa T.: "Astrocytic swelling in the ipsilateral substantia nigra after occlusion of the middle cerebral artery in rats"Brain Res.. 895. 238-214 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Narita K., Kubota M., Nakane M., Nakagomi T., Tamura A. et al.: "Therapeutic time window in the penumbra during permanent focal ischemia in rats : changes of free fatty acids and glycerophospholipids"Neurol Res.. 22. 393-400 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nakane M., Kubota M., Nakagomi T., Tamura A., Hisaki H., Shimasaki H., Ueta N.: "Lethal forebrain ischemia stimulates sphingomyelin hydrolysis and ceramide generation in the gerbil hippocampus"Neuroscience Letter. 296. 89-92 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kubota M., Nakane M., Nakagomi T., Tamura A., Hisaki H., Ueta N., Inokuchi J., Hirayama A.: "Sphingolipid biosynthesis by L-PDMP after rat MCA occlusion"Acta Neurochir (suppl). 76. 339-341 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tamura A., Nakagomi T., Kanemitsu H., Mine K. et al.: "Cerebral acetylcholine levels and long-term spatial cognitive impairment following middle cerebral artery occlusion in rats"Japan J. Psychopharmacol. 19. 267-272 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yonemori F., Yamaguchi T., Yamada H., Tamura A.: "Spatial cognitive performance after chronic focal cerebral ischemia in rats"J Cereb Blood Flor metabol. 19. 483-494 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kubota M, Nakane M, Nakagomi T, Tamura A, et al.: "Regional distribution of ethanolamine plasmalogen in the hippocampal CA1 and CA3 regions and cerebral cortex of the gerbil"Neuroscience Letter. 301. 175-178 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nakane M, Kubota M, Nakagomi T, Tamura A, et al.: "Rewarming eliminates the protective effect of cooling against delayed neuronal death"NeuroReport. 12. 2439-2442 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nakane M, Tamjura A, Miyasaka N, Nagaoka T, Kuroiwa T: "Astrocytic swelling in the ipsilateral substantia nigra after occlusion of the middle cerebral artery in rats"AJNR Am J Neuroradiol. 22. 660-663 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Zhao F, Kuroiwa T, Miyasaka N, Nagaoka T, Tamura A, et al.: "Characteristic chnages in T2-value,apparent diffusion coefficient,and ultrastructure of substantia nigra evolving exofocal postischemic neuronal death in rats"Brain Res. 895. 238-214 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] M.Nakane,M.Kubota,T.Nakagomi,A.Tamura, et al.: "Lethal forebrain ischemia stimulates sphingomyelin hydrolysis and ceramide generation in the gerbil hippocampus"Neuroscience Letters. 296. 89-92 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] K.Narita,M.Kubota,M.Nakane,S.Kitahara,T.Nakagomi,A.Tamura: "Therapeutic time window in the penumbra during permanent focal ischemia in rats : Changes of free fatty acids and glycerophospholipids"Neuro Res. 22. 393-400 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] M.Kubota,M.Nakane,T.Nakagomi,A.Tamura,H.Hisaki,S.Shimasaki: "Mild hypothermia reduces the rate of metabolism of arachidonic acid following postischemic reperfusion"Brain Res. 779. 297-300 (1998)

    • Related Report
      2000 Annual Research Report
  • [Publications] M.Kubota,K.Narita,T.Nakagomi,A.Tamura,H.Hisaki,S.Shimasaki: "Fatty acid composition of the chronic subdural hematoma : with reference to its recurrence"J.Clin.Neuroscience. 5. 63-65 (1998)

    • Related Report
      2000 Annual Research Report
  • [Publications] M.Kubota,M.Nakane,T.Nakagomi,A.Tamura,H.Hisaki,S.Shimasaki: "Sphingolipid Metabolism in Gerbil Hippocampus following Global Ischemia-Effect of Sphingolipids Synthetase Inhibitor (D-PDMP)-"J Cereb Blood Flow Metab. 19. S334 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] M.Kubota,M.Nakane,T.Nakagomi,A.Tamura,H.Hisaki,S.Shimasaki: "Sphingomyelin changes in rat cerebral cortex during focal ischemia"Neurol Res. 18. 337-341 (1996)

    • Related Report
      2000 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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