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1998 Fiscal Year Final Research Report Summary

Neuroprotection of postischemic hypothermia against ischemic neuronal damage

Research Project

Project/Area Number 09671570
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

YANASE Hisato  Ehime University, School of Medicine, Assistant, 医学部, 助手 (30243801)

Co-Investigator(Kenkyū-buntansha) KATAOKA Kiyoshi  Ehime University, School of Medicine, Professor, 医学部, 教授 (20025589)
Project Period (FY) 1997 – 1998
Keywordshypothermia / cerebral ischemia / microglia / MCA / propentofylline
Research Abstract

Many animal experiments have indicated that postischemic hypothermia rescues neurons from transient ischemic damage. The neuroprotection of postischernic hypothermia depends on initiation time, duration, temperature, as well as the degree of ischemic damage. We evaluated the neuroprotective effect of posuischemic hypothermia on ischemic damage in gerbils. Hypothermia initiated 1 hr for 11 or 23 hrs produced significant protection of CAl neurons, compared with the non-treated group. Hypothermia of 23 hrs duration greatly protected CAl neurons from death. A marked protection of CAl neurons was still observed even when hypothermia was initiated up to S hrs after ischemia. When the duration of hypothermia initiated 6 hrs after ischemia was prolonged to 24 hrs or 48 hrs after ischemia, the number of Cal neurons increased. Temperatures of hypothermia less than 35゚C (1-24 hr) were significantly neuroprotective against ischemic damage.
In the non-treated group, lectin-positive microglia first a … More ppeared 6 h after ischemia, and the strongest microglial reactions were observed 4 days after ischemia. In the short-duration (5h) postischemic hypothermia group, neuroprotections against ischemic neuronal damages were observed 7days after ischemia : However, strong microglial reactions were also observed in the short-duration postischemic hypothermia group, and most of the CAl neurons had disappeared 30 days after ischemia. In the long-duration (23h) postischemic hypothermia group, the microglial reaction was reduced throughout until 30 days after ischemia.
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 CAl neurons (60%) compared with the non-treated group (6%).
These findings indicated that the mechanisms of neuroprotection of postischemic hypothermia is partially involved in the suppression of the microglial activation after transient ischemia and that PPF has a beneficial effect on ischemic neuronal damages in the late periods after reperfusion.
in addition, we tested the neuroprotection of postischemic hypothermia in rat MCA occlusion models (lh, intraluminal method). When hypothermia started at 2, 4 or 6 h after reperfusion, the cerebral cortex infarct volume in the hypothermia group significantly decreased compared with the non-treated group. These data suggest that postischemic hypothermia is a beneficial means for cerebral protection against ischemic damages. Less

  • Research Products

    (14 results)

All Other

All Publications (14 results)

  • [Publications] Kataoka K: "Mild hypothermia-a revived countermeasure against ischemic neuronal damages" Neurosci Res. 32. 103-117 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [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
  • [Publications] 柳瀬尚人: "脳低温療法の基礎" 救急医学. 22. 895-900 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 柳瀬尚人: "グルタミン酸・カルシウム機序-細胞死の引き金としての興奮毒性" 現代医療. 30. 1351-1358 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kataoka K: "Mild brain hypothermia:potential for neuronal protection and resuscitation against ischemic damage" Biomedical Rev. 8. 23-36 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Zhang L: "Continuous monitoring and regulating of brain temperature in the conscious and freely moving ischemic gerbils:effect of MK-801 on ....." J Neurosci Res. 47. 440-448 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 片岡喜由: "低体温の脳保護作用-その歴史的あゆみと現在の基礎的治験" 日本集中治療医学会雑誌. 4. 11-17 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 柳瀬尚人: "低体温療法の歴史的背景と基礎実験の成果" 集中治療. 9. 613-624 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 柳瀬尚人: "神経細胞死と体温" 救急医学. 21. 1021-1026 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 柳瀬尚人: "脳低温療法の基礎と臨床" 総合医学社, 17 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 片岡喜由: "低体温の脳保護作用-歴史的背景と基礎的知見-" サイメッド・パブリケーションズ, 12 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kataoka K, Yanase H: "Mild hypothermia-a revived countermeasure against ischemic neuronal damage." Neurosci Res. 32. 103-117 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kataoka K, Yanase H: "Mild brain hypothermia : potential for neuronal protection and resuscitation against ischemic damage." Biomed Rev. 8. 23-36 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Zhang L, Mitani A, Yanase H, Kataoka K: "Continuous monitoring and regulating of brain temperature in the conscious and freely moving ischemic gerbil : effect of MK-801 on delayed neuronal death in hippocampal CA1." J Neurosci Res. 47. 440-448 (1997)

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

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Published: 1999-12-08  

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