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Neuroprotection of postischemic hypothermia in combination with neuroprotective agents against ischemic neuronal damage

Research Project

Project/Area Number 11671504
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Anesthesiology/Resuscitation studies
Research InstitutionEhime University

Principal Investigator

YASUGI Takumi (2000)  Ehime University, Faculty of Medicine, Assistant, 医学部, 助手 (30210248)

柳瀬 尚人 (1999)  愛媛大学, 医学部, 助手 (30243801)

Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2000: ¥1,500,000 (Direct Cost: ¥1,500,000)
Keywordshypothermia / cerebral ischemia / microglia / propentofylline / theanine / 血液脳関門 / 低体温 / 局所脳虚血
Research Abstract

Many animal experiments have indicated that postischemic hypothermia rescues neurons from transient ischemic damage. The neuroprotection of postischemic hypothermia depends on initiation time, duration, temperature, as well as the degree of ischemic damage. However, when the duration of hypothermia was only several hours and temperature was lowered only a few degrees, the neuroprotective effect of hypothermia was reduced in longer periods of survival. We examined whether short-duration or mild postischemic hypothermia in combination with neuroprotective agents treatment would consistently protect ischemic neuronal damage.
Propentofylline (PPF) is known to have an inhibitory effect of microglial proliferation. Short-duration postischemic hypothermia combined with daily PPF (10 mg/kg, ip, for 2 weeks) treatment led to a significant increase in the number of normal CA1 neurons (60%) compared with the non-treated group (6%).
γ-Glutamylethylamide (theanine) is contained in high-grade Japanese … More green tea as a natural glutamate analog. We examined the protective effect of theanine on ischemic delayed neuronal death in field CA1 of the gerbil hippocampus. One μl of theanine from each three concentrations (50 μM, 125 μM and 500 μM) was administered through the lateral ventricle 30 min before ischemia. Seven days after ischemia, the number of intact CA1 neurons in the hippocampus was assessed. Ischemic neuronal death in field CA1 of the hippocampus was significantly prevented in the theanine-pretreated groups in a dose-dependent manner, with approximately 60% and 90% survival with 125 μM and 500 μM of theanine, respectively. Moreover, we tested a protective effect of short-duration and mild hypothermia in combination with daily theanine treatment on delayed neuronal death in transient forebrain ischemia of gerbils. Theanine was administered daily 5 mg/kg after ischemia for 30 days. After survival of 30 days, the extent of CA1 neuronal damage in the hippocampus was assessed histologically. Short-duration and mild postischemic hypothermia combined with theanine treatment led to significant increase (67% and 72%, respectively) in viable CA1 neurons, compared to the control group (8% survival).
These findings indicate that short-duration and mild hypothermia in combination with PPF or theanine has a beneficial effect on ischemic neuronal damage consistently. Less

Report

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

    (26 results)

All Other

All Publications (26 results)

  • [Publications] 柳瀬尚人: "低体温によるニューロン保護の機序"医学のあゆみ. 188. 745-749 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Satoh T: "CNS-specific prostacyclin ligands as neuronal survival-promoting factors in the brain"Eur J Neurosci. 11. 3115-3124 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Cui Y: "Ischemia-induced glutamate release in the dentate gyrus : a microdialysis study in the gerbil"Neurosci Lett. 271. 191-194 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Cui Y: "Protective effect of prostaglandin I_2 analogs on ischemic delayed neuronal damage in gerbils"Biochem Biophys Res Com. 265. 301-304 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Si Q: "A serum factor enhances production of nitric oxide and tumor necrosis factor-a from cultured microglia"Exp Neurol. 162. 89-97 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 柳瀬尚人: "グルタミン酸毒性と虚血神経細胞死"Brain Medical. 12. 176-180 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 柳瀬尚人: "脳と神経-分子神経生物科学入門"共立出版. 9 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yanase H: "Brain Hypothermia"Springer-Verlag. 14 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yanase H, Kataoka K: "Mechanism of neuronal protection by hypothermia."J Clin Exp Med. 188. 745-749 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Satoh T, Ishikawa Y, Cui Y, Kataoka Y, Yanase H, Kato K, Watanabe Y, Nakadate K, Matsumura K, Hatanaka H, Kataoka K, Noyori R, Suzuki M, Watanabe Y: "CNS-specific prostacyclin ligands as neuronal survival-promoting factors in the brain."Eur J Neurosci. 11. 3115-3124 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Cui Y, Zhang L, Utsunomiya K, Yanase H, Mitani A, Kataoka K: "Ischemia-induced glutamate release in the dentate gyrus : a microdialysis study in the gerbil."Neurosci Lett. 271. 191-194 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Cui Y, Kataoka Y, Satoh T, Yamagata A, Shirakawa N, Watanabe Y, Suzuki M, Yanase H, Kataoka K: "Protective effect of prostaglandin 12 analogs on ischemic delayed neuronal damage in gerbils."Biochem Biophys Res Com. 265. 301-304 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Si Q, Nakamura Y, Kataoka K: "A serum factor enhances production of nitric oxide and tumor necrosis factor-a from cultured microglia."Exp Neurol. 162. 89-97 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yanase H, Nakamura Y: "Glutamate neurotoxicity and ischemic neuronal death."Brain Medical. 12. 176-180 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kakuda T, Yanase H, Utsunomiya K, Nozawa A, Unno T, Kataoka K: "Protective effect of γ-glutamylethylamide (theanine) on ischemic delayed neuronal death in gerbils."Neurosci Lett. 289. 189-192 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yanase H, Kataoka K: "Neuroprotective effect of mild hypothermia in experimental brain ischemia. Brain Hypothermia, Hayashi N (Ed)"Tokyo, Springer-Verlag. 69-82 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Si Q: "A serum factor enhances production of nitric oxide and tumor necrosis factor-a from cultured microglia"Exp Neurol. 162. 89-97 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 柳瀬尚人: "グルタミン酸毒性と虚血神経細胞死"Brain Medical. 12. 176-180 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kataoka Y: "Neovascularization with blood-brain barrier breakdown in delayed neuronal death"Biochem Biophys Res Com. 273. 637-641 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kakuda T: "Protective effect of γ-glutamylethylamide (theanine) on ischemic delayed neuronal death in gerbils"Neurosci Lett. 289. 189-192 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yanase H: "Brain Hypothermia"Springer-Verlag. 14 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 柳瀬尚人: "低体温によるニューロン保護の機序"医学のあゆみ. 188. 745-749 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Satoh T: "CNS-specific prostacyclin ligands as neuronal survival-promoting factors in the brain"Eur J Neurosci. 11. 3115-3124 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Cui Y: "Ischemia-induced glutamate release in the dentate gyrus:a microdialvsis study in the gerbil"Neurosci Lett. 271. 191-194 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Cui Y: "Protective effect of prostaglandin I_2 analogs on ischemic delayed neuronal damage in gerbils"Biochem Biophys Res Com. 265. 301-304 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 柳瀬尚人: "脳と神経-分子神経生物科学入門 虚血ニューロン死の本態とニューロン蘇生"共立出版. 9 (1999)

    • Related Report
      1999 Annual Research Report

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

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