Intraneuronal ion distribution during experimental oxygen/glucose deprivation. Routes of ion flux as targets of neuroprotective strategies

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Abstract

Ischemic neuronal injury appears to be mediated by disruption of subcellular ion distribution and, therefore, prevention of ion relocation might be neuroprotective. X-ray microanalysis was used to measure concentrations of Na, K, Ca and other elements in subcellular compartments (e.g., mitochondria) of CA1 neurons from oxygen/glucose-deprived (OGD) hippocampal slices. Results showed that OGD produced progressive loss of ion regulation in CA1 cells. Post-OGD reperfusion with normal media exacerbated the initial ion deregulation. To study neuroprotective mechanisms, we determined the ability of hypothermia (31°C) or ion channel blockade to retard intraneuronal ion disruption induced by OGD/reperfusion. Whereas Ca2+ channel blockade (ω-conotoxin MVIIC, 3 μM) was ineffective, hypothermia and Na+ channel blockers (tetrodotoxin, TTX, 1 μM; lidocaine, 200 μM) reduced ion deregulation in subneuronal compartments. Blockade of glutamate receptors (AMPA, 10 μM; the non-NMDA receptor antagonist CNQX, 10 μM/100 μM glycine; the NMDA receptor antagonist CCP, 100 μM) during OGD/reperfusion provided nearly complete protection. These findings provide a foundation for identifying potential pharmacotherapeutic approaches and for discerning corresponding mechanisms of neuroprotection.

Original languageEnglish (US)
Pages (from-to)191-203
Number of pages13
JournalAnnals of the New York Academy of Sciences
Volume890
StatePublished - 1999

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Ions
Oxygen
Fluxes
Glucose
Hypothermia
Reperfusion
Deregulation
Conotoxins
6-Cyano-7-nitroquinoxaline-2,3-dione
Electron Probe Microanalysis
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
Mitochondria
Relocation
Tetrodotoxin
Glutamate Receptors
Lidocaine
N-Methyl-D-Aspartate Receptors
Ion Channels
Glycine
Neurons

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

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title = "Intraneuronal ion distribution during experimental oxygen/glucose deprivation. Routes of ion flux as targets of neuroprotective strategies",
abstract = "Ischemic neuronal injury appears to be mediated by disruption of subcellular ion distribution and, therefore, prevention of ion relocation might be neuroprotective. X-ray microanalysis was used to measure concentrations of Na, K, Ca and other elements in subcellular compartments (e.g., mitochondria) of CA1 neurons from oxygen/glucose-deprived (OGD) hippocampal slices. Results showed that OGD produced progressive loss of ion regulation in CA1 cells. Post-OGD reperfusion with normal media exacerbated the initial ion deregulation. To study neuroprotective mechanisms, we determined the ability of hypothermia (31°C) or ion channel blockade to retard intraneuronal ion disruption induced by OGD/reperfusion. Whereas Ca2+ channel blockade (ω-conotoxin MVIIC, 3 μM) was ineffective, hypothermia and Na+ channel blockers (tetrodotoxin, TTX, 1 μM; lidocaine, 200 μM) reduced ion deregulation in subneuronal compartments. Blockade of glutamate receptors (AMPA, 10 μM; the non-NMDA receptor antagonist CNQX, 10 μM/100 μM glycine; the NMDA receptor antagonist CCP, 100 μM) during OGD/reperfusion provided nearly complete protection. These findings provide a foundation for identifying potential pharmacotherapeutic approaches and for discerning corresponding mechanisms of neuroprotection.",
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AU - LoPachin, Richard M.

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N2 - Ischemic neuronal injury appears to be mediated by disruption of subcellular ion distribution and, therefore, prevention of ion relocation might be neuroprotective. X-ray microanalysis was used to measure concentrations of Na, K, Ca and other elements in subcellular compartments (e.g., mitochondria) of CA1 neurons from oxygen/glucose-deprived (OGD) hippocampal slices. Results showed that OGD produced progressive loss of ion regulation in CA1 cells. Post-OGD reperfusion with normal media exacerbated the initial ion deregulation. To study neuroprotective mechanisms, we determined the ability of hypothermia (31°C) or ion channel blockade to retard intraneuronal ion disruption induced by OGD/reperfusion. Whereas Ca2+ channel blockade (ω-conotoxin MVIIC, 3 μM) was ineffective, hypothermia and Na+ channel blockers (tetrodotoxin, TTX, 1 μM; lidocaine, 200 μM) reduced ion deregulation in subneuronal compartments. Blockade of glutamate receptors (AMPA, 10 μM; the non-NMDA receptor antagonist CNQX, 10 μM/100 μM glycine; the NMDA receptor antagonist CCP, 100 μM) during OGD/reperfusion provided nearly complete protection. These findings provide a foundation for identifying potential pharmacotherapeutic approaches and for discerning corresponding mechanisms of neuroprotection.

AB - Ischemic neuronal injury appears to be mediated by disruption of subcellular ion distribution and, therefore, prevention of ion relocation might be neuroprotective. X-ray microanalysis was used to measure concentrations of Na, K, Ca and other elements in subcellular compartments (e.g., mitochondria) of CA1 neurons from oxygen/glucose-deprived (OGD) hippocampal slices. Results showed that OGD produced progressive loss of ion regulation in CA1 cells. Post-OGD reperfusion with normal media exacerbated the initial ion deregulation. To study neuroprotective mechanisms, we determined the ability of hypothermia (31°C) or ion channel blockade to retard intraneuronal ion disruption induced by OGD/reperfusion. Whereas Ca2+ channel blockade (ω-conotoxin MVIIC, 3 μM) was ineffective, hypothermia and Na+ channel blockers (tetrodotoxin, TTX, 1 μM; lidocaine, 200 μM) reduced ion deregulation in subneuronal compartments. Blockade of glutamate receptors (AMPA, 10 μM; the non-NMDA receptor antagonist CNQX, 10 μM/100 μM glycine; the NMDA receptor antagonist CCP, 100 μM) during OGD/reperfusion provided nearly complete protection. These findings provide a foundation for identifying potential pharmacotherapeutic approaches and for discerning corresponding mechanisms of neuroprotection.

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