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1997 Fiscal Year Final Research Report Summary

Signal transduction of brain capillary endothelial cells in relation to regulation of blood-brain barrier

Research Project

Project/Area Number 07671516
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Cerebral neurosurgery
Research InstitutionKobe University

Principal Investigator

NAGASHIMA Tatsuya  Kobe University, 医学部・附属病院, 講師 (80201680)

Co-Investigator(Kenkyū-buntansha) TAMAKI Norihiko  Kobe University, 医学部, 教授 (10030941)
Project Period (FY) 1995 – 1997
KeywordsBlood-brain barrier / Endothelial cells / Brain / Capilary / Signal transduction / Free radical / Calcium ion / Confocal Laser Microscopy
Research Abstract

#1 : The mechanism of reversible osmotic opening of the blood-brain barrier : role of intracellular calcium ion in capillary endothelial cells
Despite clinical and experimental interest in the osmotic opening of the blood-brain barrier (BBB), the mechanism underlying the phenomenon remain undermined. The aim of this study is to investigate the mechanism of intracellular calcium ion change in brain microvascular endothelial cells subjected to hyperosmotic stress.
MATERIALS AND METHODS : Cultured rat brain capillary endothelial cells were obtained by two-step enzymatic purification. Intracellular calcium ion was measured by a confocal laser scanning microscope. After exposing the endothelial cells to 1.4 M mannitol, the change of intracellular calcium ion concentration was monitored.
RESULTS : Intracellular calcium ion concentration increased rapidly and reached its peak value within 10 seconds after the application of mannitol. The calcium ion concentration returned to the basal level with … More in 200 seconds. A specific blocker (KB-R7943) of sodium/calcium exchange did not affect the rapid elevation of intracellular calcium ion. However, it blocked the return phase almost completely. The results indicated that the sodium/calcium exchanger pumped out the increased intracellular sodium/calcium during the return phase.
CONCLUSION : Reversible osmotic disruption and reconstruction of the BBB is not due to simple mechanical shrinkage of the endothelial cells but is due to the intracellular calcium ion-activated complex mechanism.
#2 : Mechanism of BBB Disruption in Reoxygenation Injury of Rat Brain Capillary Endothelial Cells
MATERIALS AND METHODS : Rat and human BCEC were subjected to anoxia/reoxygenation. Enzyme inhibitors including oxypurinol, indomethacin, or L-NAME,or specific free-radical scavengers such as superoxide dismutase (SOD), catalase, or the ferric iron chelator deferoxamine were added before A/R injury. The BCEC were incubated in a range of calcium ion concentrations from 1 mM to 0.01 mM during A/R injury. Cytotoxicity was assayd by release of intracellular lactate dehydrogenase (LDH).
RESULTS : With A/R injury, LDH release from the control group (no protective agents) significantly increased compared with a small increase in a normoxic group. BCEC treated with oxypurinol, indomethacin, or L-NAME showed suppression of LDH release. LDH release was almost totally suppressed by SOD,and partially by catalase or deferoxamine. The LDH release was partly dependent on calcium concentration.
CONCLUSION : BCEC subjected to A/R become potent generators of free radicals, especially superoxide anion. Free radical production depends on both xanthine oxidase and cyclooxygenase pathways. Peroxynitrite and extracellular calcium ion both contribute importantly to reoxygenation injury of BCEC. Less

  • Research Products

    (13 results)

All Other

All Publications (13 results)

  • [Publications] Wu S, Nagashima T.: "Reactive oxygen species in reoxygenation injury of rat brain capillary endothelial cells" Neurusugery 1998. (in press). (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Suzuki H, Nagashima T.: "Cerebral ischemia affects glucose transporter kinetics across rat brain microvascular endothelium" Surgical Neurology. 49. 67-76 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Wu S, Nagashima T.: "Effect of superoxide dismutase,catalase and allopurinol on reoxigenated cultured human brain endothelial cells" J Cell Molecular Neurobiol,1998. (in press). (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Wu S, Nagashima T.: "The mechanism free radical genaration in brain capillary endothelial cells after anoxia and reoxigenation" Acta Neurochir(supl). 70. 37-39 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ikeda K, NagashimaT: "The role of calcium ionin anoxia/reoxygenation damage of cultured brain capillary endothelial cells" Acta Neurochir(supl). 70. 4-7 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nagashima T, et al: "The mechanism of reversible osmotic opening of bloo-brain barrier a role of intracellular caluium ion" Acta Neurochir(supl). 70. 231-233 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Wu S,Nagashima T,et al.: "Reactive oxygen species in reoxygenation injury of rat brain capillary endothelial cells" Neurusugery. (in press). (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Suzuki H,Nagashima T,et al.: "Cerebral ischemia affects glucose transpoter kinetics across rat brain microvascular endothelium" Surgical Neurology. 49. 67-76 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Miyake S,Nagashima T,et al.: "Idiopathic spinal cord herniation : report of two cases and review of the literature" J of Neurosurgery. 88. 331-335 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Wu S,Nagashima T,et al.: "Effect of superoxide dismutase, catalase and allopurinol on reoxigenated cultured human brain endothelial cells" J Cell Molecular Neurobiol. (in press). (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Wu S,Nagashima T,et al.: "The mechanism free radical generation in brain capillary endothelial cells after anoxia and reoxigenation" Acta Neurochir (supl). 70. 37-39 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ikeda K,Nagashima T,et al.: "The role of calcium ionin anoxia/reoxygenation damage of cultured brain capillary endothelial cells" Acta Neurochir (supl). 70. 4-7 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nagashima T,Wu S,et al.: "The mechanism of reversible osmotic opening of blood-brain barrier : a role of intracellular calcium ion" Acta Neurochir (supl). 70. 231-233 (1997)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1999-03-16  

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