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1998 Fiscal Year Final Research Report Summary

Neuron-Glia Interaction and Neural Network Function Involved in Ischemic Brain Damage.

Research Project

Project/Area Number 09680817
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 神経・脳内生理学
Research InstitutionHamamatsu University School of Medicine (1998)
Nagoya City University (1997)

Principal Investigator

FUKUDA Atsuo  Hamamatsu University School of Medicine, Physiology, Professor, 医学部, 教授 (50254272)

Co-Investigator(Kenkyū-buntansha) NISHINO Hitoo  Nagoya City Univ.Med.Sch., Physiology, Professor, 医学部, 教授 (60073730)
UCHIDA Katsuhisa  Hamamatsu Univ.Sch.Med., Physiology, Res.Assoc., 医学部, 助手 (10168693)
SAMEJIMA Michikazu  Hamamatsu Univ.Sch.Med., Physiology, Assoc.Prof., 医学部, 助教授 (80135251)
Project Period (FY) 1997 – 1998
KeywordsIntracellular Cl^- / Cl^- transporter / MEQ / Intracellular Ca^<2+> / Na^+-Ca^<2+> exchanger / Cerebral ischemia / Mitochondria / Glia
Research Abstract

1. Slices of neocortex taken from P7-14 rats were labeled with fura-2. The [Ca^<2+>] _i was monitored pyramidal cells during O_2-glucose deprivation. Neurons in layer II/III showed significantly greater increases in [Ca^<2+>] _i than those in layers IV, V, or VI.The laminar difference in terms of the [Ca^<2+>] _i increases was primarily mediated by NMDA receptors. GABA might also act to increase [Ca^<2+>] _i during O_2-glucose deprivation. After a reduction in the Cl^- gradient, GABA induced a large [Ca^<2+>] _i increase mediated by NMDA receptor-channels. This indicates that a loss of the normal Cl^- gradient during ischemia might underlie the reduction and/or reversal of the GABAergic inhibition. Thus GABA may play an aggravating role in excitotoxicity if a shift in the Cl^- equilibrium potential occurs during cerebral ischemia.
2. We have developed an optical imaging method of [Cl^-] _i in brain slices using 6-methoxy-N-ethylquinolinium iodide (MEQ). Slices of neocortex taken from P1 … More 0-14 rats were labeled with MEQ ; [Cl^-] ^i was monitored in individual neurons during O_2-glucose deprivation. A slight decrease followed by rather abmpt increase in [Cl^-] _i was induced by O_2-glucose deprivation. The former was mediated by an inhibition of Na^+, K^+-2Cl^- cotransporter. Such a shift in [Cl^-] _i induced by O_2-glucose deprivation would alter the GABAergic inhibition and may result in imbalance between inhibitory and excitatory systems.
3.3-NPA-induced [Ca^<2+>] _i transients in mixed glial/neuronal cultures were investigated using fura-2.3-NPA irreversibly increased [Ca^<2+>] _i in astrocytes, but significantly to alesser extent in neurons. The [Ca^<2+>] _i increase in astrocytes was primarily promoted by a reverse operation of the Na^+-Ca^<2+> exchanger system, whereas in neurons, it was mediated by a different mechanism. In addition, 3-NPA killed 9% of astrocytes, while only 4% of neurons. This astrocytic cell death was preceded by blebbing of membranes and by abrupt [Ca^<2+>] _i surge following sustained [Ca^<2+>] _i increase. The results indicate that astrocytes are more vulnerable than neurons to 3-NPA-induced cellular Ca^<2+> overload and toxicity. Differential metabolism in energy production between astrocytes and neurons were suggested. Less

  • Research Products

    (27 results)

All Other

All Publications (27 results)

  • [Publications] Muramatsu, K.et al.: "Topography of hypoxic injury proved by argyrophilia in postnatal rat brain." Pediatric Neurology. 16. 105-113 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Deshpande, S.B.et al.: "3-Nitropropionic acid increases the intracellular Ca^<2+> in cultured astrocytes by reverse operation of Na^+-Ca^<2+> exchanger." Experimental Neurology. 145. 38-45 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nishino, H.et al.: "Acute 3-nitropropionic acid intoxication induces striatal astrocytic cell death and dysfunction of the blood-brain barrier : involvement of dopamine toxicity." Neuroscience Research. 27. 343-35〓 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hida, H.et al.: "Dopamine-denervation enhances the trophic activity in striatum : evaluation by morphological and electrophysiological development in PC12D cells." Neuroscience Research. 28. 209-221 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Muramatsu, et al.: "Vulnerability to cerebral hypoxic-ischemic insult in neonatal but not in adultrats is in parallel with disruption of the blood-brain barrier." Stroke. 28. 2281-2289 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shimano, Y.et al.: "Spatio-temporal pattern of dysfunction of the blood-brain barrier in the striatum after systemic intoxication with 3-nitropropionic acid (a mitochondrial toxin)." Journal of Brain Science. 23. 167-180 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Fukuda, A.et al.: "NMDA receptor-mediated differential laminar susceptibility to the intracellular Ca^<2+> accumulation induced by oxygen-glucose deprivation in rat neocortical slices." Journal of Neurophysiology. 79. 430-438 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Fukuda, A.et al.: "Changes in intracellular Ca^<2+> induced by GABA_A receptor activation and reduction in Cl^- gradient in neonatal rat neocortex." Journal of Neurophysiology. 79. 439-446 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Farkas, I.et al.: "Neuronal C5a recetor and an associated apoptotic signal transduction pathway." Journal of Physiology. 507. 679-688 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Fukuda, A.et al.: "Astrocytes are more vulnerable than neurons to cellular Ca^<2+> overload induced by a mitochondrial toxin, 3-nitropropionic acid." Neuroscience. 87. 497-507 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nishino, H.et al.: "Estrogen protects against while testosterone exacerbates vulnerability of the lateral striatal artery to chemical hypoxia by 3-nitropropionic acid." Neuroscience Research. 30. 303-312 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Fukuda, A.et al.: "Simultaneous optical imaging of intracellular Cl^- in neurons in different layers of rat neocortical slices : advantages and limitations." Neuroscience Research. 32. 363-371 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 福田 敦夫 (分担): "脳機能の解明-21世紀に向けて-(赤池紀扶,他 編)" 九州大学出版会, 615 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kumazaki, M.et al.: "Mitochondrial inhibitors as a tool for neurobiology(Sanberg et al., eds.)" Humana Press (in press),

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Muramatsu, K.et al.: "Topography of hypoxic injury proved by argyrophilia in postnatal rat brain." Pediatric Neurology. 16. 105-113 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Deshpande, S.B.et al.: "3-Nitropropionic acid increases the intracellular Ca^<2+> in cultured astrocytes by reverse operation of Na^+-Ca^<2+> exchanger." Experimental Neurology. 145. 38-45 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nishino, H.et al.: "Acute 3-nitropropionic acid intoxication induces striatal astrocytic cell death and dysfunction of the blood-brain barrier : involvement of dopamine toxicity." Neuroscience Research. 27. 343-355 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hida, H.et al.: "Dopamine-denervation enhances the trophic activity in striatum : evaluation by morphological and electrophysiological development in PC12D cells." Neuroscience Research. 28. 209-221 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Muramatsu, et al.: "Vulnerability to cerebral hypoxic-ischemic insult in neonatal but not in adult rats is in parallel with disruption of the blood-brain barrier." Stroke. 28. 2281-2289 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shimano, Y.et al.: "Spatio-temporal pattern of dysfunction of the blood-brain barrier in the striatum after systemic intoxication with 3-nitropropionic acid (a mitochondrial toxin)." Journal of Brain Science. 23. 167-180 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Fukuda, A.et al.: "NMDA receptor-mediated differential laminar susceptibility to the intracellular Ca^<2+> accumulation induced by oxygen-glucose deprivation in rat neocortical slices." Journal of Neurophysiology. 79. 430-438 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Fukuda, A.et al.: "Changes in intracellular Ca^<2+> induced by GABA_A receptor activation and reduction in Cl^- gradient in neonatal rat neocortex." Journal of Neurophysiology. 79. 439-446 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Farkas, I.et al.: "Neuronal C5a recetor and an associated apoptotic signal transduction pathway." Journal of Physiology. 507. 679-688 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Fukuda, A.et al.: "Astrocytes are more vulnerable than neurons to cellular Ca^<2+> overload induced by a mitochondrial toxin, 3-nitropropionic acid." Neuroscience. 87. 497-507 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nishino, H.et al.: "Estrogen protects against while testosterone exacerbates vulnerability of the lateral striatal artery to chemical hypoxia by 3-nitropropionic acid." Neuroscience Research. 30. 303-312 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Fukuda, A.et al.: "Simultaneous optical imaging of intracellular Cl^- in neurons in different layers of rat neocortical slices : advantages and limitations." Neuroscience Research. 32. 363-371 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kumazaki, M.et al.: "Humana Press. Mitochondrial inhibitors as a tool for neurobiology (Sanberg et al., eds.)" (in press).

    • 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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