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Changes of sphingosine-1-phosphate in delayed neuronal death

Research Project

Project/Area Number 09671411
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Cerebral neurosurgery
Research InstitutionUniversity of Tokyo

Principal Investigator

KAWAI Kensuke  University of Tokyo Faculty of Medicine Assistant, 医学部・附属病院, 助手 (70260924)

Co-Investigator(Kenkyū-buntansha) FUJIMAKI Takamitsu  University of Tokyo Faculty of Medicine Assistant, 医学部・附属病院, 助手 (80251255)
IDE Takafumi  University of Tokyo Faculty of Medicine Assistant, 医学部・附属病院, 助手 (40262000)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1998: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1997: ¥2,400,000 (Direct Cost: ¥2,400,000)
Keywordsdelayed neuronal death / cerebral ischemia / sphingosine-1-phosphate / gerbil
Research Abstract

The present project aims to elucidate the role of sphingosine-1-phosphate (Sph-1-P) in the pathway of delayed neuronal death in CA1 neuronal cells. While Sph-1-P has recently been reported to have an important role in intracellular calcium release as an intracellular messenger, the role of Sph-1-P is unknown in ischemic delayed neuronal death, in which increase of intracellular calcium concentraion is a pivotal step toward cell death.
First, we have established the assay system for Sph-1-P and examined Sph-1-P contents in various regions of the brains of normal control gerbils. We extracted Sph-1-P by ice cold chloroform/methanol (1 : 2) and measured it by HPLC and radioimmunoassay. The Sph-1-P contents measured by radioimmunoassay in the hippocampus, cerebral cortex and cerebellum were 5.42*1.90, 0.84*0.21, 4.29*1.67 nmol/mg (mean*SEM, n=5), respectively. Measurement by HPLC could not give sufficient sensitivity and Sph-1-P was not detected in the hippocampus and cerebral cortex.
Then, … More we examined changes in Sph-1-P contents in the brains after transient cerebral ischemia. Male mongolian gerbils (60-8Og) were subjected to 5 minute forebrain ischemia. Bilateral carotidarteries were occluded with aneurysmal clips for 5 min under halothane anesthesia. The rectal and temporal muscle temperatures were controlled at 37.5゚C using heating lamp and blanket. Brains were removed from gerbils before ischemia, 6 hours, 12 hours, 24 hours, and 48 hours after ischemia and Sph-1-P contents in the hippocampus, cerebral cortex and cerebellum were determined by above-mentioned method The Sph-1-P contents in the regions were as follows. Values are presented in the order of ; before ischemia, 6 hours, 12 hours, 24 hours, and 48 hours after ischemia.
Hippocapmus : 5.42*1.90, 4 63*1.24, 4.62*1.55, 4.89*1.73 (nmol/mg, mean*SEM, n=5)
Cerebral cortex : 0.84*0.21, 0.67*0.19, 0.72*0.12, 0.63*0.15 (nmol/mg, mean*SEM, n=5)
Cerebellum : 4.29*1.67, 4.56*1.71, 6.04*1.37, 6.34*2.26 (nmol/mg, mean*SEM, n=5)
Thus, no chronological changes were found in the Sph-1-P contents after ischemia.
These results suggested that Sph-1-P is not involved in the pathological pathway of neuronal death in CA1 regions. However, the present assay system could not allow cell-specific, or intracellular site-specific measurement of Sph-1-P and whether intracellular local changes of Sph-1-P are associated with cell death pathway should await further studies. Less

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (21 results)

All Other

All Publications (21 results)

  • [Publications] Kawai K,Nakagomi T,Kirino T,Tamura A,Kawai N.: "Preconditioning in vivo ischemia inhibits anoxic LTP and functionally protects CA1 neurons in the gerbil." J Cereb Blood Flow Metab. 18. 288-296 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kawahara N,Ide T,Saito N,Kawai K,Kirino T.: "Propentofylline potentiates induced ischemic tolerance in gerbil hippocampal neurons via adenosine receptor." J Cereb Blood Flow Metab. 18. 472-475 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kawai K,Nakayama H,Tamura A.: "Limited but significant protective effect of hypothermia on ultra-early-type ischemic neuronal injury in the thalamus." J Cereb Blood Flow Metab. 17. 543-552 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nakanishi H,Tamura A,Kawai K,Yamamoto K.: "Electrophysiological studies of rat substantia nigra neurons in an in vitro slice preparation after middle cerebral artery occlusion." Neuroscience. 77. 1021-1028 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Furuya K,Kawai K,Asai A,Tamura A.: "Growth-associated protein GAP-43 detection in the neuronal somata following middle cerebral artery occlusion in the rat." Neurol Res. 19. 160-164 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 川合謙介,桐野高明: "前脳虚血モデルにおける低脳温効果." 集中治療9:627-634,1997. 9. 627-634 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kawai K,Nakagomi T,Kirino T,Tamura A,Kawai N.: "Preconditioning in vivo ischemia inhibits anoxic LTP and functionally protects CA1 neurons in the gerbil." J Cereb Blood Flow Metab. 18. 288-296 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kawahara N,Ide T,Saito N,Kawai K,Kirino T.: "Propentofylline potentiates induced ischemic tolerance in gerbil hippocampal neurons via adenosine receptor." J Cereb Blood Flow Metab. 18. 472-475 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kawai K,Nakayama H,Tamura A.: "Limited but significant protective effect of hypothermia on ultra-early-type ischemic neuronal injury in the thalamus." J Cereb Blood Flow Metab. 17. 543-552 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nakanishi H,Tamura A,Kawai K,Yamamoto K.: "Electrophysiological studies of rat substantia nigra neurons in an in vitro slice preparation after middle cerebral artery occlusion" Neuroscience. 77. 1021-1028 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Furuya K,Kawai K,Asai A,Tamura A.: "rowth-associated protein GAP-43 detection in the neuronal somata following middle cerebral artery occlusion in the rat." Neurol Res. 19. 160-164 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kawai K,Kirino T.: "Effect of hypothermia in forebrain ischemia models.(in Japanese)" Intensive Care Medicine. 9. 627-634 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kawai K,Nakagomi T,Kirino T,Tamura A,Kawai N.: "Preconditioning in vivo ischemia inhibits anoxic LTP and functionally protects CAI neurons in the gerbil." J Cereb Blood Flow Metab. 18. 288-296 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kawahara N,Ide T,Saito N,Kawai K,Kirino T.: "Propentofylline potentiates induced ischemic tolerance in gerbil hippocampal neurons via adenosine receptor." J Cereb Blood Flow Metab. 18. 472-475 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kawai K,Nakayama H,Tamura A.: "Limited but significant protective effect of hypothermia on ultra-early-type ischemic neuronal injury in the thalamus." J Cereb Blood Flow Metab. 17. 543-552 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Nakanishi H,Tamura A,Kawai K,Yamamoto K.: "Electrophysiological studies of rat substantia nigra neurons in an in vitro slice preparation after middle cerebral artery occlusion." Neuroscience. 77. 1021-1028 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Furuya K,Kawai K,Asai A,Tamura A.: "Growth-associated protein Gap-43 detection in the neuronal somata following middle cerebral artery occlusion in the rat." Neurol Res. 19. 160-164 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] 川合謙介,桐野高明: "前脳虚血モデルにおける低脳温効果." 集中治療. 9. 627-634 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ide T, Morikawa E , Kirino T: "An immunosuppressant,FK506,protects hippocampal neurons from forebrain ischemia in the Mongolian gerbil" Neuroscience Letters. 204. 157-160 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kensuke Kawai, Hitoshi Nakayama, Akira Tamura: "Limited but significant protective effect of hypothermia on ultra-early-type ischemic neuronal injury in the thalamus" Journal of Cerebral Blood Flow and Metabolism. 17. 543-552 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 川合謙介、桐野高明: "前脳虚血モデルにおける低脳温効果" 集中治療-Intensive & Critical Care Medicine-. 9. 627-634 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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