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Effects of anesthesia related drugs on neuronal apoptosis : alterations of enzymatic activities elicited by intracellular calcium elevation.

Research Project

Project/Area Number 13671562
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Anesthesiology/Resuscitation studies
Research InstitutionGunma University

Principal Investigator

SAITO Sigeru  GUNMA UNIVERSITY, School of Medicine, Associate professor, 医学部, 助教授 (40251110)

Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 2003: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2002: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2001: ¥900,000 (Direct Cost: ¥900,000)
Keywordslocal anesthetics / nerve growth cone / growth cone collapse / neurotoxicity / neurotrophic factor / intracellular calcium concentration / 細胞内カルシウム / テトラカイン / アポトーシス
Research Abstract

Local anesthetics impair morphology of neurons and disturb physiological nerve conduction. Especially, lidocaine and tetracaine are most toxic among the commercially available local anesthetics. Apoptosis is one of the basic mechanism of the neurotoxity, however, recent publications described that the toxicity could not be thoroughly explained by apoptosis. Growth cones at the tip of growing neurons have been demonstrated as labile to the neurotoxicity of local anesthetics. Several neurotrophic factors promote the recovery of neurons that are exposed to local anesthetics. In the present study, we have demonstrated that mepivacaine, bupivacaine and ropivacaine have similar neurotoxity to growth cones and growing neurites, and that neurotrophic factors, NT-3, BDNF, GDNF, have potential to promote neuronal survival and regeneration following the injury by local anesthetics. Intracellular calcium ion elevation was observed after the exposure to tetracaine beginning from the tip of growing neurite. The way of elevation was not spiky but slowly elevating, and implied impairment of membrane integrity.

Report

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

    (23 results)

All Other

All Publications (23 results)

  • [Publications] Radwan IA, Saito S, Goto F.: "Neurotrophic factors can partially reverse morphological changes induced by mepivacaine and bupivacaine in developing sensory neurons."Anesth Analg.. 97巻2号. 506-511 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kadoi Y, Hinohara H, Kunimoto F, Saito S, Ide M, Hiraoka H, Kawahara: "Diabetic patients have an impaired cerebral vasodilatory response to hypercapnia under propofol anesthesia."Stroke.. 34巻10号. 2399-2403 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kadoi Y, Saito S, Kunimoto F, Goto F, Fujita N.: "Comparative effects of propofol versus fentanyl on cerebral oxygenation state during normothermic cardiopulmonary bypass and postoperative cognitive dysfunction."Ann Thorac Surg.. 75巻3号. 840-846 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Radwan IA, Saito S, Goto F.: "Growth cone collapsing effect of lidocaine on DRG neurons is partially reversed by several neurotrophic factors."Anesthesiology.. 97巻3号. 630-635 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Radwan IA, Saito S, Goto F.: "The neurotoxicity of local anesthetics on growing neurons : a comparative study of lidocaine, bupivacaine, mepivacaine, and ropivacaine."Anesth Analg.. 94巻2号. 319-324 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Saito S, Radwan I, Obata H, Takahashi K, Goto F.: "Direct neurotoxicity of tetracaine on growth cones and neurites of growing neurons in vitro."Anesthesiology.. 95巻3号. 726-733 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Radwan IA, Saito S, Goto F.: "Neurotrophic factors can partially reverse morphological changes induced by mepivacaine and bupivacaine in developing sensory neurons."Anesth Analg.. 97-2. 506-511 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kadoi Y, Hinohara H, Kunimoto F, Saito S, Ide M, Hiraoka H, Kawahara F, Goto F.: "Diabetic patients have an impaired cerebral vasodilatory response to hypercapnia under propofol anesthesia."Stroke. 34-10. 2399-2403 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kadoi Y, Saito S, Kunimoto F, Goto F, Fujita N.: "Comparative effects of propofol versus fentanyl on cerebral oxygenation state during normothermic cardiopulmonary bypass and postoperative cognitive dysfunction."Ann Thorac Surg.. 75-3. 840-846 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Radwan IA, Saito S, Goto F.: "Growth cone collapsing effect of lidocaine on DRG neurons is partially reversed by several neurotrophic factors."Anesthesiology. 97-3. 630-635 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Radwan IA, Saito S, Goto F.: "The neurotoxicity of local anesthetics on growing neurons : a comparative study of lidocaine, bupivacaine, mepivacaine, and ropivacaine."Anesth Analg.. 94-2. 319-324 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Saito S, Radwan I, Obata H, Takahashi K, Goto F.: "Direct neurotoxicity of tetracaine on growth cones and neurites of growing neurons in vitro."Anesthesiology. 95-3. 726-733 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Radwan IA, Saito S, Goto F: "Neurotrophic factors can partially reverse morphological changes induced by mepivacaine and bupivacaine in developing sensory neurons."Anesth Analg.. 97巻・2号. 506-511 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kadoi Y, Hinohara H, Kunimoto F, Saito S, Ide M, Hiraoka H, Kawahara F, Goto F: "Diabetic patients have an impaired cerebral vasodilatory response to hypercapnia under propofol anesthesia."Stroke.. 34巻・10号. 2399-2403 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kadoi Y, Saito S, Kunimoto F, Goto F, Fujita N: "Comparative effects of propofol versus fentanyl on cerebral oxygenation state during normothermic cardiopulmonary bypass and postoperative cognitive dysfunction."Ann Thorac Surg.. 75巻・3号. 804-846 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Inas AM Radwan, Shigeru Saito, Fumio Goto: "The neurotoxicity of local anesthetics on growing neurons : a comparative study of lidocaine, bupivacaine, mepivacaine, and ropivacaine"Anesth Analg. 94巻・2号. 319-324 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Radwan IA, Saito S, Goto F.: "Growth cone collapsing effect of lidocaine on DRG neurons is partially reversed by several neurotrophic factors"Anesthesiology. 97巻・3号. 630-635 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Shigeru Saito, 他: "Direct Neurofoxicity of Tetracaine on Growth Cones and Neurites of Growing Neurons in vitro"Anesthesiology. 95・9. 726-733 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hideaki Obata, Shigeru Saito, 他: "Antiallodynic Effect of Jutrathecally Administered 5-HT2 Agonists in Rats With Nerve Ligation"Pain. 90・1-2. 173-179 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nara T., Saito S., 他: "A Rat Model of Postthracotomy pain : Behavicural and Spinal Cord NK-1 Receptor Assessment"Canadian Journal of Anaesthesiology. 48・7. 665-676 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kadoi Y., Saito S., 他: "Decrease in Jugular Venous Oxygen Saturation During Normothermic Cardiopulmonary Bypass Predicts Short-term Postoperative Neurologic Dysfunction in Elderly Patients"Journal of American Colledge of Cardiology. 38・5. 1450-1455 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Radwan I., Saito S., 他: "High Concentration Tetracaine for the Management of Trigeminal Neuralgia : Quantitative Assessment of Sensory Function After Peripheral Nerve Block"The Clinical Journal of Pain. 17・4. 323-326 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Radwan I., Saito S., 他: "The Neurotoxicity of Local Anesthetics on Growing Neurons : A Comparative Study of Lidocaine, Bupivacaine, Mepivacaine, and Repivacaine"Anesthesia & Analgesia. 94(印刷中). (2002)

    • Related Report
      2001 Annual Research Report

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

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