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The research for the mechanism of ischemic cell damage in the striatum and the restoration of the neuronal basic circuit by neural transplantation

Research Project

Project/Area Number 03454352
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Cerebral neurosurgery
Research InstitutionNagoya City University Medical School

Principal Investigator

NAGAI Hajime  Nagoya City University Medical School, Neurosurgery, Professor, 医学部, 教授 (00023747)

Co-Investigator(Kenkyū-buntansha) NISHINO Hitoo  Nagoya City University Medical School, Physiology, Professor, 医学部, 教授 (60073730)
MABE Hideo  Nagoya City University Medical School, Neurosurgery, Assistant Professor, 医学部, 助教授 (20093073)
Project Period (FY) 1991 – 1992
Project Status Completed (Fiscal Year 1992)
Budget Amount *help
¥6,700,000 (Direct Cost: ¥6,700,000)
Fiscal Year 1992: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1991: ¥5,700,000 (Direct Cost: ¥5,700,000)
KeywordsIschema / Striatum / Transplantaion / 移植 / 学習能 / 神経伝達物質 / 脳虚血 / 脳内移植 / 運動学習能 / 神経回路網 / 機能修復
Research Abstract

(1) An increase of extracellular release of striatal dopamine and glutamate was observed during total and focal cerebral ischemia. A D1 receptor antagonist and destruction of substantial nigra which caused decrease of striatal dopamine release prevented ischemic cell damage in the striatum. These results suggest that extracellular dopamine release in the striatum during ischemia may contribute to ischemic cell damage. A Phospholipase C inhibitor which decreased the release of arachidonic acid in the early period of ischemia decreased extracellular glutamate release in the striatum. These results suggest that the release of arachidonic acid may cause further release of glutamate in the striatum in the early period of ischemia.
(2) We implanted cell suspensions of fetal striatum into ischemic region caused by intraluminal occlusion of middle cerebral artery in the rat, and investigated survival/development of grafted cells and functional recovery. Transplantation reversed the ischemia induced behavioral deficits in the passive avoidance task and water-maze test. Dendritic outgrowth marked with Dil(1,1'-dioctadecyl-3,3,3-',3-'tetramethylindo-carbocyanine perchlorate) could be seen under fluorescent microscopy. Immunohistochemical study revealed that many ChAT(choline acetyltransferase) positive cells and GABA positive cells survived. GABA level in the globus pallidus was decreased 1 month after ischemia. Transplantation normalized the GABA level in the globus pallidus. Autoradiography revealed that muscarinc, D1, D2 and GABA receptors were developed in the grafts. Data suggest that fetal striatal cell grafting remodels the ischemic brain and ameliorates damaged functions. However, anatomical and physiological connections between the grafts and hosts could not be observed in this study. Therefore, further investigations are needed.

Report

(3 results)
  • 1992 Annual Research Report   Final Research Report Summary
  • 1991 Annual Research Report
  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] 相原 徳孝,小出 和雄: "神経移植と学習機能の再建" Clinical Neuroscience. 10. 1008-1010 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 西野 仁雄,小出 和雄,相原 徳孝,永井 肇: "脳神経移植による機能の修復ー虚血性脳障害への応用ー" 脳卒中. 14. 794-797 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Koide.K,Hashitaui T,Aihara N,et al: "Improuement of passine auoidance task after grafting of fetal〜" Restor,Neurol.Neurosci. (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Nishino H,Koide K,Aihara N,et al: "Stviatal grafts in the ischemic stviafum improvement pallidal GABA〜" Brain Res.Bull. (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] N.Shimo H,Aihara N,Czurko A,etal: "Recmstructin of GABergic transnissin and behauior by〜" J.Newal Trasp.Plast.(1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Aihara, N. and Koide, K.: "Neural Transplantation and Restoration of learnig function" Clinical Neuroscience. Vol.10,No.9. (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Nishino, H., Koide, K., Aihara, N. and Nagai, H.: "Mechanisms of functional recovery in neural transplantation -Application to ischemia brain damages-" Jpn j Stroke. 14. 794-797 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Koide, K., Hashitani, T., Aihara, N., Made, H. and Nishino, H.: "Improvement of passive avoidance task after grafting of fetal striatal cell suspension in ischemic striatum in the rat" Restor. Neurol. Neurosci.(1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Nishino, H., Koide, K., Aihara, N., Kumazaki, M., Sakurai, T., and Nagai, H.: "Striatal grafts in the ischemic striatum improve pallidal GABA release and passive avoidance." Brain Res. Bull.(1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Nishino, H., Aihara, N., Czurko, A., Hashitanio T., Isobe, Y., Ichikawa, O. and Watari, H.: "Reconstruction of GABAergic transmission and behavior by striatal cell grafts in rats with ischemic infarcts in the middle cerebral artery" J. Neural Transp. Plast.(1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 谷村 一、永井 肇、梅村 淳: "脳虚血時の脳内アラキドン酸とglutamateとの相関" 第17回日本脳卒中学会総会抄録集. 182- (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 相原 徳孝、水川 公直、小出 和雄、間部 英雄、永井 肇、西野 仁雄: "ラット虚血線条体梗塞巣への胎仔線条体細胞の移植による学習能の回復" 第17回日本脳卒中学会総会抄録集. 207- (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] K.Koide,H.Hagai,K.Mabe,T.Hashitani N.Aihara,H.Nishino: "Striatal cell grafts in ischemic region following intraluminal occulusion of middle cerebral aitery ameliorate cytoarchitectual,chemical and behanoral dam age(PartI)" Sewnd world congress of stroke 抄録集. S89- (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] N.Aihara K.Mizukawa K.Koide H.Mabe H.Nagai,H.Nishino: "Striatal cell grafts in ishemic region following infraluminal occulusion of middle cerebral aitery ameliorate cytoarchi cectm chenicul and behavioral damage Part2)" SECOND WORLD CONGRESS OF STROKE 抄録集. S84- (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 相原 徳孝 小出 和雄: "神経移植と学習機能の再建" CLINICAL NEUROSCIENCE. 10. 1008-1010 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 小出 和雄,橋本 信和,金井 秀樹,間部 英雄,永井 肇,端谷 毅,熊崎 路子,西野 仁雄: "ラット虚血線条体梗塞巣への胎仔線条体細胞の移植による運動学習の回復" 神経組織の成長・再生・移植研究会 第5回学術集会論文集. 2. 80-81 (1990)

    • Related Report
      1991 Annual Research Report
  • [Publications] 橋本 信和,小出 和雄,松本 隆,間部 英雄,永井 肇,端谷 毅,西野 仁雄: "線条体虚血細胞死に対するdopamine拮抗薬の効果" 日本脳卒中学会機関誌. 13. 552 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 相原 徳孝,水川 公直,小出 和雄,間部 英雄,永井 肇,西野 仁雄: "ラット虚血線条体梗塞巣への胎仔線条体細胞の移植による学習能の回路ーGABA mergic nevronに注目してー" 神経組織の成長・再生・移植研究会 第6回学術集会論文集. 3. 20-21 (1991)

    • Related Report
      1991 Annual Research Report

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Published: 1991-04-01   Modified: 2016-04-21  

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