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Neuroprotective effects of mild hypothermia on brain injuries basic and clinical research on learning and functional disturbances

Research Project

Project/Area Number 12470291
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Cerebral neurosurgery
Research InstitutionKagawa Medical School

Principal Investigator

NAGAO Seigo  Kagawa University, Neurosurgery, Professor, 医学部付属病院, 教授 (60100947)

Co-Investigator(Kenkyū-buntansha) KAWAI Nobuyuki  Kagawa University, Neurosurgery, Lecturer, 医学部付属病院, 講師 (40294756)
Project Period (FY) 2000 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥7,000,000 (Direct Cost: ¥7,000,000)
Fiscal Year 2002: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 2001: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 2000: ¥2,600,000 (Direct Cost: ¥2,600,000)
KeywordsBrain hypothermia / Cerebral ischmeia / Acute subdural hematoma / Intracerebral hemorrhage / Blood-brain barrier / Polymorphonuclear leukocytes / Brain edema / Rats / 脳低温療法 / 脳浮腫 / Matrix Metalloroteinase / 低体温療法 / 機能障害 / 重症脳損傷 / 脳虚血(局所) / 脳出血 / 多核白血球 / インターロイキン1β / intercellular adhesion molecule-1 (ICAM-1)
Research Abstract

We have investigated the neuroprotective effects of mild brain hypothermia on various injury models in rodents. In a model focal cerebral ischemia in rats, intraischemic and postischemic hypothermia significantly reduced the volume of infarction at 24 hours after ischemia. This protection was accompanied with significant reduction of polymorphonuclear (PMN) leukocytes infiltration into the injured-brain. In a model of acute subdural hematoma in rats, mild hypothermia with intravenous administration of alkalizing agent significantly protected the blood-brain barrier (BBB) from breakdown and reduced the brain edema formation. This treatment also reduced the size of infarction under the hematoma 7 days after the hematoma induction. In a model of intracerebral hematoma, mild hypothermia significantly protected the BBB from the breakdown and reduced the brain edema formation 24 hours after the induction of hematoma or thrombin. Mild hypothermia significantly reduced the infiltration of PMN leukocytes into the brain. Ina model of transient forebrain ischemia in gerbils, mild hypothermia almost completely protected the neurons in hippocampus from the neuronal death 7 days after the ischmeia but not completely protected the neurons 1 month after the ischemia. Combined treatment with mild hypothermia and NMDA receptor antagonist protected these neurons from the delayed death. In this project, we confirmed the protective effects of mild brain hypothermia on several brain injury models in rodents. These results will help the clarification the neuroprotective mechanisms of brain hypothermia and enhance the application of brain hypothermia in clinical settings

Report

(4 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (31 results)

All Other

All Publications (31 results)

  • [Publications] N.Kawai, M.Okauchi, K.Morisaki, S.Nagao: "Effect of delayed intraischemic and postischemic hypothermia on a focal model of transient cerebral ischemia rats"Stroke. 31. 1982-1989 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] N.Kawai, M.Kawanishi, M.Okauchi, S.Nagao: "Effect of hypothermia on thrombin-induced brain edema formation"Brain Research. 895. 50-58 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] T.Nakamura, N.Tatara, K.Morisaki, K.Kawakita, N.Kawai, S.Nagao: "Cerebral oxygen metabolism monitoring under hypothermia for severe subarachnoid hemorrhage"Proceedings of the 9th Annual Meeting of the Society for Treatment of Coma. 9. 51-55 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] T.Nakamura, O.Miyamoto, N.Kawai, T.Negi, T.Itano, S.Nagao: "Long-term activation of the glutamatergic system associated with NMDA receptors after postischemic hypothermia in gerbils"Neurosurgery. 49. 706-714 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M.Okauchi, N.Kawai, T.Nakamura, M.Kawanishi, S.Nagao: "Effects of Mild Hypothermia and Alkalizing Agents on Brain Injuries in Rats with Acute Subdural Hematomas"Journal of Neurotrauma. 19. 741-751 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 中村丈洋, 山下史朗, 河井信行, 國塩勝三, 長尾省吾, 中野通代, 小倉真治, 宮本 修, 板野俊文: "低体温療法における導入および復温時での体温変化による神経細胞への影響についての実験的検討"神経外傷. 25. 48-52 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nobuyuki Kawai, Takehiro Nakamura, Masanobu Okauchi, Seigo Nagao: "Effects of Hypothermia on Intracranial Pressure and Brain Edema Formation : Studies in a Rat Acute Subdural Hematoma Model"J Neurotrauma. 17. 193-02 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nobuyuki Kawai, Takehiro Nakamura, Masanobu Okauchi, Seigo Nagao: "Effect of Hypothermia on Intracranial Hemodynamics and Ischemic Brain Damage-Studies in the Rat Acute Subdural Hematoma Model"Acta Neurochir. 76. 529-533 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nobuyuki Kawai, Masanobu Okauchi, Kuniaki Morisaki, Seigo Nagao: "Effect of delayed intraischemic and postischemic hypothermia on a focal model of transient cerebral ischemia rats"Stroke. 31(8). 1982-1989 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nobuyuki Kawai, Masahiko Kawanishi, Masanobu Okauchi, Seigo Nagao: "Effect of hypothermia on thrombin-induced brain edema formation"Brain Research. 895. 50-58 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takehiro Nakamura, Naoto Tatara, Kuniaki Morisaki, Kenya Kawakita, Nobuyuki Kawai, Seigo Nagao: "Cerebral oxygen metabolism under hypothermia for severe consciousness disturbance after subarachnoid hemorrhage"Proceedings of the 9th Annual Meeting of the Society for Treatment of Coma. 9. 51-55 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takehiro Nakamura, Osamu Miyamoto, Nobuyuki Kawai, Tetsuro Negi, Toshifumi Itano, Seigo Nagao: "The long-term activation of glutamatergic system associated with NMDA receptor following post-ischemic hypothermia in gerbils"Neurosurgery. 49. 706-714 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nobuyuki Kawai, Takehiro Nakamura, Seigo Nagao: "Effects of Brain Hypothermia on Brain Edema Formation after Intracerebral Hemorrhage in Rats"Acta Neurochir. (Suppl) 81. 233-235 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Masanobu Okauchi, Nobuyuki Kawai, Takehiro Nakamura, Masahiko Kawanishi, Seigo Nagao: "Effects of Mild Hypothermia and Alkalizing Agents on Brain Injuries in Rats with Acute Subdural Hematomas"Journal of Neurotrauma. 19(6). 741-751 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takehiro Nakamura, Naoto Tatara, Kuniaki Morisaki, Kenya Kawakita, Seigo Nagao: "Cerebral oxygen metabolism monitoring under hypothermia for severe subarachnoid hemorrhage : report of eight cases"Acta Neurol Scand. 106. 314-318 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] N.Kawai, T.Nakamura, S.Nagao: "Effects of Brain Hypothermia on Brain Edema Formation after Intracerebral Hemorrhage in Rats"Acta Neurochir (Suppl). 81. 233-235 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Masanobu Okauchi, Nobuyuki Kawai, Takehiro Nakamura, Masahiko Kawanishi, Seigo Nagao: "Effects of Mild Hypothermia and Alkalizing Agents on Brain Injuries in Rats with Acute Subdural Hematomas"Jounal of Neurotrauma. 19. 741-751 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 河井信行, 中村丈洋, 長尾省吾: "脳虚血に対する低体温療法"脳神経外科. 30. 1273-1283 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 中村丈洋, 山下史朗, 河井信行, 國塩勝三, 長尾省吾, 中野通代, 小倉真治, 宮本 修, 板野俊文: "低体温療法における導入および復温時での体温変化による神経細胞への影響についての実験的検討"神経外傷. 25. 48-52 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 中村丈洋, 山下史朗, 河井信行, 國塩勝三, 宮本 修, 板野俊文, 長尾省吾: "実験的脳損傷後における神経再生の可能性についての検討"脳循環代謝. 14. 208-209 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 河井信行, 岡内正信, 中村丈洋, 川西正彦, 長尾省吾: "一時的ラット局所脳虚血モデルにおける虚血後脳低温療法の脳損傷に対する長期保護効果"脳循環代謝. 14. 112-113 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] T.Nakamura, O.Miyamoto, N.Kawai, T.Negi, T.Itano, S.Nagao: "The long-term activation of glutamatergic system associated with NMDA receptor following post-isehemic hypothermia in gerbils"Neurosurgery. 49. 706-714 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] S.Nagao, K.Irie, N.Kawai, T.Ogawa, T.Nakamura, M.Okauchi: "Protective effect of mild hypothermia on symptomatic vasospasm : A preliminary report"Acta Neurochir(Wein)suppl. 76. 547-550 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] 中村丈洋, 宮本 修, 山神眞一, 岡内正信, 河井信行, 板野俊文, 長尾省吾: "実験的脳挫傷モデルにおける低体温およびマンニトールによる抗浮腫効果の検討:脳浮腫・頭蓋内圧研究会報告集"脳浮腫・頭蓋内圧研究会報告集3, 15-20, 2001. 3. 15-20 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 中村丈, 山下史朗, 岡内正信, 河井信行, 國塩勝三, 長尾省吾, 宮本 修, 板野俊文: "実験的頭部外傷後における神経再生の可能性-組織学的および神経行動学的検討-"神経外傷. 24. 8-62 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] N.Kawai, T.Nakamura, M.Okauchi, S.Nagao: "Effects of hypothermia on intracranial hemodynamics and isehernic brain damage-studies in the rat acute subdural hematorna model"Acta Neurochir(Wein)suppl. 76. 529-533 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] N.Kawai, T.Nakamura, M.Okauchi, S.Nagao: "Effects of hypothermia on thrombin-induced brain edema formation"Brain Research. 895. 50-58 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 武田則昭: "A県下国保レセプトにみる地域医療需給状況-3大疾病(悪性新生物、脳血管疾患、虚血性心疾患)の入院・外来医療-"Supplement to Journal of Epidemiology. 11・1. 66 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] 岩瀬哲也: "大学附属病院所在地M町における地域医療需給状況の変遷(老人保健法施行直後、公的介護保険施行直後の15年) その1 K県国保レセプトにみる3大疾病(悪性新生物、脳血管疾患、虚血性心疾患)の外来医療"病院管理学会雑誌. 37・Suppl. 153 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 武田則昭: "大学附属病院所在地M町における地域医療需給状況の変遷(老人保健法施行直後、公的介護保険施行直後の15年) その2 K県国保レセプトにみる3大疾病(悪性新生物、脳血管疾患、虚血性心疾患)の入院医療"病院管理学会雑誌. 37・Suppl. 154 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 川田久美: "K県国保レセプトからみた地域医療需給状況の変遷(老人保健法施行直後と公的介護保険施行直後の15年) その1 悪性新生物の入院医療"病院管理学会雑誌. 37・Suppl. 155 (2000)

    • Related Report
      2000 Annual Research Report

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

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