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Effects of active oxygen scavengers on the occurrence of epileptic foci in a rat model of post -traumatic epilepsy

Research Project

Project/Area Number 13671447
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Cerebral neurosurgery
Research Institution大分医科大学

Principal Investigator

YOKOI Isao  Oita University, Faculty of Medicine, Professor, 医学部, 教授 (80150366)

Co-Investigator(Kenkyū-buntansha) KUBOTA Hideaki  Kagawa Prefectural College of Health Science, Faculty of Health Science, Lecturer, 保健医療学部, 講師 (00321266)
KITANO Takaaki  Oita University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (20211196)
YAMADA Naoko (NISIMARU Naoko)  Oita University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (60101086)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2003: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2002: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2001: ¥2,100,000 (Direct Cost: ¥2,100,000)
Keywordsposttraumatic epilepsy model / epileptic EEG / prevention of epileptic foci formation / hemoglobin / hydroxyl radical scavengers / melatonin / zinisamide / ascorbyl radical / 外傷性てんかん / 外傷性てんかんモデル / ヘモグロヒン / 細胞膜流動性 / EPC-K1
Research Abstract

Head injury results in extravasation of blood and breakdown of red blood cells and hemoglobin (Hb). Iron liberated from Hb, and Hb itself also, is to be associated with generation of free radicals (FRs). FRs have been demonstrated to be involved in the mechanism of seizures induced by iron ion injection into the rat brain, an experimental animal model for posttraumatic epilepsy (PTE). In this study, FRs formation in the brain during convulsions and effects of FRs scavengers, such as melatonin and zonisamide (ZNS), on the occurrence of epileptogenic foci formation were examined. An experimental model for PTE was made by [lb injection into the rat brain. Experimental results were as follows :
1.The typical ascorbyl radical (Asc-R) signal was detected clearly in the hippocampal slices, and increased during kainate-induced seizures. Antiepileptic ZNS inhibited significantly the occurrence of convulsions and generation of Asc -R.
2.We developed a more specific and economical detecting method of Asc -R.
3.Positive poly-spikes were started in electrocorticograms (ECoG) of rat.3 days after Hb injection with twitching of vibrissae synchronized with spike activity.
4.The percent induction of epileptic discharges in ECoGs was not changed in rats given ZNS-contained diet for 2 months after Hb injection. Daily intake of ZNS-contained diet was significantly lower.
5.Rats were given melatonin in drinking water for 3 months after [lb injection. However, the percent induction of epileptic discharges was not changed. There were some rats showed transient weight loss.
This is the first observation of Asc-R in the brain induced by seizures with an ESR spectrometry, and Asc-R was increased in the hippocamps during kainate-induced seizures, suggesting an excess generation of FRs in the brain. However, we failed to show the effects of antioxidants on epileptic focus formation because of unexpected low diet intake and transient weight loss

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (22 results)

All Other

All Publications (22 results)

  • [Publications] 横井 功: "てんかんとフリーラジカル"Clinical Neuroscience. 19. 575-577 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 横井 功: "てんかんの基礎研究-最近の動向"脳21. 4. 226-230 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hideaki Kabuto, Isao Yokoi, Norio Ogawa, Akitane Mori, Robert P.Liburdy: "Effects of magnetic fields on the accumulation of thiobarbituric acid reactive substances induced by iron salt and H_2O_2 in mouse brain homogenates or phosphotidylcholine."Pathophysiology. 7. 283-288 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nihei Yamamoto, Hideaki Kabuto, Sigekiyo Matsumoto, Norio Ogawa, Isao Yokoi: "α-Tocopheryl-L-ascorbate-2-O-phosphate diester, a hydroxyl radical scavenger, prevents the occurrence of epileptic foci in a rat model of post-traumatic epilepsy."Pathophysiology. 8. 205-214 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Takaaki Kitano, Naoko Nisimaru, Eriko Hayashi, Hideo Iwasaka, Takayuki Noguchi, Isao Yokoi: "Monocarboxylates and glucose utilization as energy substrates in rat brain slices under selective glial poisoning- a^<31>P NMR study."Mol.Cell.Biochem.. 244. 77-81 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shigekiyo Matsumoto, Toshiki Masumizu, Eriko Shibata, Isao Yokoi: "Role of ascorbyl radicals iv the hippocampus during kainic acid-induced seizures in mice : An electron spin resonance study"Jpn.J.Physiol.. 53(Suppl.). S325 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Toshiki Masumizu, Yasuko Noda, Isao Yokoi, Akitane Mori: "Ascorbyl radical generation in the rodent hippocampus during kainate-induced seizures : Au electron spine sesonance. (ESR) study."Free Rad.Biol.Med.. 35 Suppl.1. S159 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Akitane Mori, Isao Yokoi, Yasuko Noda, L.James Willmore: "Natural antioxidants may prevent posttraumatic epilepsy : A proposal based on experimental animal studies."Acta Med.Okayama. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Isao Yokoi: "Free radicals in epilepsy"Clinical Neuroscience (in Japanese). 19-5. 575-577 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Isao Yokoi: "Basic research on epilepsy : up-to-date"Brain 21 (in Japanese). 4-3. 226-230 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hideaki Kabuto, Isao Yokoi, Norio Ogawa, Akitane Mori, Robert P.Liburdy: "Effects of magnetic fields on the accumulation of thiobarbituric acid reactive substances induced by iron salt and H_20_2 in mouse brain homogenates or phosphotidyicholine."Pathophysiology. 7. 283-288 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nihei Yamamoto, Hideaki Kabuto, Sigekiyo Matsumoto, Norio Ogawa, Isao Yokoi: "α-Tocopheryl-L-ascorbate-2-O-phosphate diester, a hydroxyl radical scavenger, prevents the occurrence of epileptic foci in a rat model of post-traumatic epilepsy."Pathophysiology. 8. 205-214 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Takaaki Kitano, Naoko Nisimaru, Eriko Hayashi, Hideo Iwasaka, Takayuki Noguchi, Isao Yokoi: "Monocarboxylates and glucose utilization as energy substrates in rat brain slices under selective glial poisoning-a^<31>P NMR study."Mol. Cell. Biochem.. 244. 77-81 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Toshiki Masumizu, Yasuko Noda, Isao Yokoi, Akitane Mori: "Ascorbyl radical generation in the rodent hippocampus during kainate-induced seizures : An electron s pine sesonance (ESR) study."Free Rad. Biol. Med.. 35(Suppl.1). S159 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shigekiyo Matsumoto, Toshiki Masumizu, Eriko Shibata Isao Yokoi: "Role of ascorbyl radicals in the hippocampus during kainic acid-induced seizures in mice : An electron spin resonance study."Jpn. J. Physiol.. 53(Suppl.). S325 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Akitane Mori, Isao Yokoi, Yasuko Noda, L.James Willmore: "Natural antioxidants may prevent posttraumatic epilepsy: A proposal based on experimental animal studies."Acta Med. Okayama. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Akitane Mori, Toshiki Masumizu, Isao Yokoi, Lester Packer: "Kainic acid-induced neurotoxicity : Involvement of free radicals"Moecular Interventions & Protection in Lyfestyle Related Diseases. (In press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nihei Yamamoto, Hideaki Kabuto, Sigekiyo Matsumoto, Norio Ogawa, Isao Yokoi: "α-Tocopheryl-_L-ascorbate-2-O-phosphate diester, a hydroxyl radical scavenger, prevents the occurrence of epileptic foci in a rat model of post-traumatic epilepsy"Pathophysiology. 8. 205-214 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 横井 功: "日本てんかん学会"大分県医師会会報. 577. 32-33 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 横井 功: "てんかんの基礎的研究-最近の動向"脳21. 4・3. 12-16 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 横井 功: "フリーラジカルと神経疾患:てんかんとフリーラジカル"Clinical Neuroscience. 19・5. 77-79 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nihei Yamamoto, Hideaki Kabuto, Sigekiyo Matsunoto, Norio Ogawa, Isao Yokoi: "a-Tocopheryl-L-ascorbate-2-O-phosphate diester, a hydroxyl radical scavenger, prevents the occurrence of epileptic foci in a rat model of post-traumatic epilepsy"Pathophysiology. (印刷中).

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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