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Radical scavengers as preventive preparations of post-traumatic epilepsy

Research Project

Project/Area Number 05671164
Research Category

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

Allocation TypeSingle-year Grants
Research Field Cerebral neurosurgery
Research InstitutionOkayama University

Principal Investigator

YOKOI Isao  Okayama Univ.Med.Sch.Associate professor, 医学部, 助教授 (80150366)

Project Period (FY) 1993 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1995: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1994: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1993: ¥700,000 (Direct Cost: ¥700,000)
Keywordspost-traumatic epilepsy / active oxygens / radical scavengers / (-) -epigallocatechin / EPC / adenosine / nitric oxide synthase / nitric oxide / 活性酸素消去剤 / 活性酸素 / グアニジノ化合物 / メチルグアニジン / 活性酵素 / エピガロカテキンガレート / 脳透析 / 神経伝達物質
Research Abstract

After intracranial hemorrhage, iron ions are liberated by the breakdown of red blood cells, and then active oxygens are generated in brain tissue by iron-mediated reactions. These radicals form an convulsive guanidino compounds, and also may be responsible for the initiation of lipid peroxidation in neural membranes. Injury to the membranes impairs neuronal activity and causes disrupts neuro-transmission. These disorders may lead to early seizures, which is a major risk factor for the development of post-traumatic epilepsy. Therefore, when active oxygens are removed from the focal area, the subsequent steps may not occur and the formation of epileptic foci may be avoided.
In the present studies, I focused on the effects of some radical scavengers, such as (-) -epigallocatechin (EGC), EGC-3-O-gallate (EGCG), _L-ascorbic acid 2- [3,4-di-hydro-2,5,7,8-tetramethyl-2- (4,8,12-trimethyltridecyl) -2H-1-benzopyran-6-yl hydrogen phosphate] potassium salt (EPC), adenosine (Ado) and 2-chloroadenos … More ine (Cl-Ado), on physiological and neurochemical changes in an experimental model of post-traumatic epilepsy induced by ferric chloride injction. To suppress the occurrence of epileptic discharges induced by FeCl_3 injection, (1)EGC and EGCG inhibit dopaminergic hyperactivity via activation of serotonergic neurones and production of convulsive guanidino compounds, (2)EPC activated suppressive dopaminergic neurons, and (3)Ado and Cl-Ado scavenged active oxygens. It might is accompanied with formation of an epileptic focus that nitric oxide synthase (NOS), of which product may act as an endogenous anticonvulsant, decreased.
I conclude that the occurrence of post-traumatic epilepsy may be prevented by using active oxygen scavengers as preventive preparations. Active oxygens have been also suggested to be involved in a number of human disease processes such as cancer, ischemia, epilepsy, aging, and other diseases. Therefore, these active oxygen scavengers may also be useful as a clinical agent in the prevention, treatment and the attenuation of such free radical-induced degenerative diseases. Less

Report

(4 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • 1993 Annual Research Report
  • Research Products

    (37 results)

All Other

All Publications (37 results)

  • [Publications] 横井 功: "外傷性てんかんとフリーラジカル。" J. Act. Oxyg. Free Rad.4. 620-626 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 横井 功: "Up data フリーラジカル-基礎と臨床:脳。" 現代医療. 25. 3365-3370 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 森 昭胤: "免疫とストレス:中枢神経系と酸素ストレス。" Medical Immunology. 26. 540-550 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 羽部 仁: "マウス脳内窒素酸化物量の検討。" Neurosciences. 19. 165-168 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Isao Yokoi: "Structure activity relationships of arginine analogues on nitric oxide synthase activity in the rat brain." Neuropharmacol.33. 1261-1265 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Hitoshi Habu: "Application of automated flow injection analysis to determine nitrite and nitrate in mouse brain." NeuroReport. 5. 1571-1573 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 横井 功: "2-塩化アデノシンによる外傷性てんかん発症予防に関する研究。" Neurosciences. 20. P161-P164 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Isao Yokoi: "Adenosines scavenged hydroxyl radicals and prevented post-traumatic epilepsy." Free Rad. Biol. Med.19. 473-479 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 横井 功: "脳疾患におけるFree Radicalの役割。" 脳と神経. 47. 1039-1049 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Isao Yokoi: "EPC, a new active oxygen free radical acavenger, prevents the occurrence of epileptic discharges in a rat model of post-traumatic epilepsy." (発表予定).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Hideaki Kabuto: "Nitric oxide synthase activity reduced with development of an epileptogenic focus induced by ferric chloride in rat brain." (発表予定).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Akitane Mori: "Oxidative stress and damage as the pathogenesis of epilepsy. In : Oxidative Stress and Aging," R. Cutler, L. packer, J. Bertram & A. Mori (Eds.), Birkhauser Verlag, Basel,9 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 森 昭胤: "てんかんの神経生化学。In:てんかんの最新外科治療、" 朝倉哲彦(監修)、朝倉哲彦、菊地晴彦、森竹治三(編)、医学書院、東京, 3 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Isao Yokoi: "Redical scavengers as preventive preparations of post-traumatic epilepsy. In : Free Radicals in Brain and Disorders," L. Packer, M. Hiramatsu & T. Yoshikawa (Eds.) Academic Press (in press),

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Isao Yokoi: "Structure activity relationships of guanidino compounds on brain nitric oxide synthase activity. In: Guanidino Compounds in Biology and Medicine II," I. A. Qureshi, B. Marescau, P. P. De Deyn & A. Mori (Eds.), John Libbey, London (in press),

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] I.Yokoi: "Free radicals and post-traumatic epilepsy." J.Act.Oxyg.Free Rad.4. 620-626 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] I.Yokoi, et al.: "Free radicals-basi and clinical implications." Gendai Iryou. 25. 3365-3370 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] A.Mori, et al.: "Oxidative stress and central nervous system." Medical Immunology. 26. 540-550 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] H.Habu, et al.: "Determination od nitrogen oxide in mouse brain." Neurosciences. 19. 165-168 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yokoi, et al.: "Structure activity relationships of arginine analogues on nitric oxide synthase activity in the rat brain." Neuropharmacol.33. 1261-1265 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Habu, et al.: "Application of automated flow injection analysis to determine nitrite and nitrate in mouse brain." NeuroReport. 5. 1571-1573 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] I.Yokoi, et al.: "2-Chloroadenosine prevents the occurrence of epileptic discharges in a rat model of post-traumatic epilepsy." Neurosciences. 20. 161-164 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] I.Yokoi, et al.: "Adenosines scavenged hydroxyl radicals and prevented post-traumatic epilepsy." Free Rad.Biol.Med.19. 473-479 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] I.Yokoi, et al.: "Free radicals and neurological disorders." Brain and Nerve. 47. 1039-1049 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] I.Yokoi, et al.: "EPC,a new active oxygen free radical scavenger, prevents the occurrence of epileptic discharges in a rat model of post-traumatic epilepsy." (in preparation).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] H.Kabuto, et al.: "Nitric oxide synthase activity reduced with development of an epileptogenic focus induced by ferric chloride in rat brain." (in preparation).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] A.Mori, et al.: "Oxidative stress and damage as the pathogenesis of epilepsy." In : Oxidative Stress and Aging.R.Cutler, et al.eds., Birkhauser Verlag, Basel. 309-317 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] A.Mori et al.: "Neurochemistry of epilepsy." In : Today's Neurosurgical Therapy of Epilepsy. I.Asakura (ed.), Igaku Shoin, Tokyo. 18-20 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] I.Yokoi, et al.: "Radical scavengers as preventive preparations of post-traumatic epilepsy." In : Free Radicals in Brain and Disorders, L.Packer, et al.eds., Academic Press. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] I.Yokoi, et al.: "Structure activity relation-ships of guanidino compounds on brain nitric oxide syntthase activity." In : Guanidino Compounds in Biology and Medicine II,I.A.Qureshi, et al.eds., John Libbey & Co.Ltd., London. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 横井 功: "Adenosines scavenged hydroxyl radicals and prevented post-traumatic epilepsy." Free Rad.Biol.Med.19. 473-479 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 横井 功: "脳疾患におけるFree Radicalの役割" 脳と神経. 47. 1039-1049 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 横井功、加太英明、羽部仁、劉健康、当真純二、岩谷和夫、森昭胤: "2-塩化アデノシンによる外傷性てんかん発症予防に関する研究" Neurosciences. 20. 161-164 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 横井 功: "外傷性てんかんとフリーラジカル" 活性酸素・フリーラジカル. 4. 620-626 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 森 昭胤: "免疫とストレス:中枢神経系と酸素ストレス" Medical Immunology. 26. 540-550 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 横井 功: "Up dataフリーラジカル-基礎と臨床:脳" 現代医療. 25. 3365-3370 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 横井 功: "2-塩化アデノシンによる外傷性てんかん発症予防に関する研究。" Neurosciences. 20 (印刷中). (1994)

    • Related Report
      1993 Annual Research Report

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Published: 1993-04-01   Modified: 2016-04-21  

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