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1998 Fiscal Year Final Research Report Summary

Extracellular neurotransmitter release and generation of reactive oxygen species during cerebral ischemia-reperfusion

Research Project

Project/Area Number 08671757
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Anesthesiology/Resuscitation studies
Research InstitutionUniversity of the Ryukyus

Principal Investigator

YUSA Toshiko  Univ.of the Ryukyus Associate Professor, 医学部, 助教授 (30032329)

Project Period (FY) 1996 – 1998
Keywordscerebral ischemia-reperfusion / extracellular glutamate release / neurotransmitter / nitric oxide / hyperbaric oxygen / free radicals / shock / rat brain
Research Abstract

Excessive release of excitatory amino acids such as glutamate and increased generation of free radicals such as reactive oxygen species (ROS) and nitric oxide (NO) are involved in mechanisms of cerebral damage during ischemia-reperfusion. Therefore extracellular glutamate release and NO generation were measured in vivo with microdialysis biosensor and microdialysis in rat forebrain isohemia - reperfusion model. Forebrain ischemia-reperfusion was performed by bilateral carotid artery occlusion (10 min) with controlled hemorrhagic hypotension (MAP = 30 mmHg). NO generation was determined by measuring NO end-products (nitrite and nitrate). The effect of hyperbaric oxygen (HBO) on generation of NO and ROS was also determined in rat model, where NO and ROS had been considered to increase (endotoxin injection, hemorrhagic shock and hyperbaric CNS oxygen toxicity).
1) Extracellular glutamate and NO release, and effects of NO synthase (NOS) inhibitor (L-NAME)
a) Extracellular glutamate levels in striatum, hippocampus and forebrain cortex increased biphasically upto about 6-fold during ischemia and returned to the baseline level within 30 mm after reperfusion. b) Nitrite increased during schemia and 40 min after reperfusion, however, nitrate changed in the opposite direction. c) NOS inhibition by L-NAME did not prevent ischemia-induced glutamate release, and increased glutamate level during reperfusion.
2) Effect of HBO on generation of NO and ROS
a) HBO did not suppress increased plasma levels of NO-endproducts (nitrite, nitrate) in endotoxin-treated rats. HBO significantly increased plasma nitrite and nitrate level in rats of hemorrhagic shock, which was induced by withdrawing blood until MAP = 40 mmHg for 30 mm and thereafter replaced by plasma expander. HBO, however, prolonged survival time compared to control rats. b) As the results of experiments using NO and ROS related agents, increased generation of NO and ROS take part in oxygen toxicity induced by HBO in ONS.

  • Research Products

    (30 results)

All Other

All Publications (30 results)

  • [Publications] 湯佐祚子: "活性酸素・フリーラジカルとスカベンジャー" 日本高気圧環境医学会雑誌. 31. 153-167 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nohara A,Yusa T: "Reversibility in blood-brain barrier, microcirculation, and histology in rat brain after decompression." Undersea & Hyperbaric Medicine. 24. 15-21 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 砂川昌秀, 佐祚子: "エンドトキシン投与ラットでの血中硝酸・亜硝酸の変動に及ぼす高気圧酸素の影響" 麻酔. 46. 1447-1453 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 湯佐祚子: "高気圧酸素療法の物理と生理" ICUとCCU. 21. 833-839 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 湯佐祚子: "前脳虚血-再灌流の脳血流量及びglutamate遊離に及ぼす影響とnitric oxideの関与について." Journal of Anesthesia. 10. 521 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 野原敦,湯佐祚子: "中枢性酸素中毒に及ぼす活性酸素とNitric Oxideの影響" 日本高気圧環境医学会雑誌. 31. 33 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yusa T: "Effects of ischemia-reperfusion and nitric oxide synthase (NOS) inhibition on cerebral blood flow (CBF) and glutamate release." Abstract of 11th Word Congress of Anaesthesiologists.262 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 湯佐祚子: "前脳虚血-再灌流の活性酸素(hydrogen peroxide)及びglutamateの細胞外遊離に及ぼす影響" Journal of Anesthesia. 11. 344 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 中村清哉, 湯佐祚子, 上運天均: "人口心肺使用中のnitrite, nitrateの変動" 日本臨床麻酔学会誌. 17. S149 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 砂川昌秀,湯佐祚子,西川洋介: "出血性ショック及びその後の貧血に対する高気圧酸素療法の影響-血中NO_2^-/NO_3^-及び動脈圧の変化-" 日本高気圧環境医学会雑誌. 32. 45 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 野原敦,湯佐祚子: "中枢性酸素中毒に及ぼすNOの影響" 日本高気圧環境医学会雑誌. 32. 45 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 湯佐祚子: "前脳虚血-再灌流によるnitric oxide及びglutamateの細胞外遊離への影響" Journal of Anesthesia. 12. 159 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 湯佐祚子,砂川昌秀: "出血性ショックでのnitric oxideの関与-高気圧酸素及びdexamethasoneの影響-" Journal of Anesthesia. 12. 374 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yusa T,Sunagawa M: "Involvement of nitric oxide in hemorrhagic ahock -effect of hyperbaric oxygen and dexamethasone-." Anesthesiology. 88. A398 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 與座浩次,湯佐祚子,大城匡勝: "CABG患者での人口心肺使用中のnitrite, nitrateの変動" 日本臨床麻酔学会誌. 18. S159 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yusa T: "Reactive oxygen species, free radicals and their scavengers in relation to oxygen toxicity." The Japanese Journal of Hyperbaric Medicine. 31. 153-167 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nohara A, Yusa T: "Reversibility in blood-brain barrier, microcirculation, and histology in rat brain after decompression." Undersea & hyperbaric Medicine. 24. 15-21 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sunagawa M, Yusa T: "The effect of hyperbaric oxygen on nitrite and nitrate production in rats treated with endotoxin." Masui. 46. 1447-1453 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yusa T: "Physical and physiological aspects of hyperbaric oxygenation." ICU & CCU. 21. 833-839 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yusa T: "Effects of forebrain ischemia-reperfusion and nitric oxide on cerebral blood flow and glutamate release." J Anesthesia. 10 (suppl). 521 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nohara A.Yusa T: "Effects of reactive oxygen soecies and nitric oxyde on CNS oxygen toxicity." The Japanese Journal of Hyperbaric Medicine. 31. 33 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yusa T: "Effects of ischemia-reperfusion and nitric oxide synthase (NOS) inhibition on cerebral blood flow (CBF) and glutamate release." Abstract of 11th World Congress of Anesthesiologists. 262 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yusa T: "Effects of forebrain ischemia-reperfusion on extracellular hydrogen peroxide and glutamate release." J Anesthesia. 11. 344 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakamura S, Yusa T, Kamiunten H: "Changes in plasma nitrite and nitrate during Cardiopulmonary bypass." The Journal of Japan Society for Clinical Anesthesia. 17. S149 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sunagawa M, Yusa T, Nishikawa Y: "Effect of hyperbaric oxygenation on hemorrhagic shock-changes in plasma NO_2^-/NO_3^- and arterial blood pressure" The Japanese Journal of Hyperbaric Medicine. 32. 45 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nohara A, Yusa T: "Effect of NO production on CNS oxygen toxicity." The Japanese Journal of Hyperbaric Medicine. 32. 45 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yusa T: "Effects of forebrain ischemia-reperfusion on extracellular nitric oxide and glutamate release" J Anesthesia. 12. 159 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yusa T, Sunagawa M: "Role of nitric oxide in hemorrhagic shock-effects of hyperbaric oxygen and dexamethasone-" J Anesthesia. 12. 374 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yusa T, Sunagawa M: "Involvement of nitric oxide in hemorrhagic shock-effect of hyperbaric oxygen and dexanethasone-." Anesthesiology. 88. A398 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoza K, Yusa T, Ohshiro M: "Changes in plasma nitrite and nitrate of patients undergone CABG with cardiopulmonary bypass." The Journal of Japan Society for Clinical Anesthesia. 18. S159 (1998)

    • 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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