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Chloride transport inhibitors influence recovery from oxygen-glucose deprivation-induced cellular injury in adult hippocampus.

Publication ,  Journal Article
Pond, BB; Galeffi, F; Ahrens, R; Schwartz-Bloom, RD
Published in: Neuropharmacology
August 2004

Cerebral ischemia in vivo or oxygen-glucose deprivation (OGD) in vitro are characterized by major disturbances in neuronal ionic homeostasis, including significant rises in intracellular Na(+), Ca(2+), and Cl(-) and extracellular K(+). Recently, considerable attention has been focused on the cation-chloride cotransporters Na-K-Cl cotransporter isoform I (NKCC-1) and K-Cl cotransporter isoform II (KCC2), as they may play an important role in the disruption of ion gradients and subsequent ischemic damage. In this study, we examined the ability of cation-chloride transport inhibitors to influence the biochemical (i.e. ATP) and histological recovery of neurons in adult hippocampal slices exposed to OGD. In the hippocampus, 7 min of OGD caused a loss of ATP that recovered partially (approximately 50%) during 3 h of reoxygenation. Furosemide, which inhibits the NKCC-1 and KCC2 cotransporters, and bumetanide, a more specific NKCC-1 inhibitor, enhanced ATP recovery when measured 3 h after OGD. Furosemide and bumetanide also attenuated area CA1 neuronal injury after OGD. However, higher concentrations of these compounds appear to have additional non-specific toxic effects, limiting ATP recovery following OGD and promoting neuronal injury. The KCC2 cotransporter inhibitor DIOA and the Cl(-) ATPase inhibitor ethacrynic acid caused neuronal death even in the absence of OGD and promoted cytochrome c release from isolated mitochondria, indicating non-specific toxicities of these compounds.

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Published In

Neuropharmacology

DOI

ISSN

0028-3908

Publication Date

August 2004

Volume

47

Issue

2

Start / End Page

253 / 262

Location

England

Related Subject Headings

  • Solute Carrier Family 12, Member 2
  • Solute Carrier Family 12, Member 1
  • Sodium Potassium Chloride Symporter Inhibitors
  • Rats, Sprague-Dawley
  • Rats
  • Neurons
  • Neurology & Neurosurgery
  • Male
  • In Vitro Techniques
  • Hypoxia
 

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Pond, B. B., Galeffi, F., Ahrens, R., & Schwartz-Bloom, R. D. (2004). Chloride transport inhibitors influence recovery from oxygen-glucose deprivation-induced cellular injury in adult hippocampus. Neuropharmacology, 47(2), 253–262. https://doi.org/10.1016/j.neuropharm.2004.04.002
Pond, Brooks B., Francesca Galeffi, Rebecca Ahrens, and Rochelle D. Schwartz-Bloom. “Chloride transport inhibitors influence recovery from oxygen-glucose deprivation-induced cellular injury in adult hippocampus.Neuropharmacology 47, no. 2 (August 2004): 253–62. https://doi.org/10.1016/j.neuropharm.2004.04.002.
Pond BB, Galeffi F, Ahrens R, Schwartz-Bloom RD. Chloride transport inhibitors influence recovery from oxygen-glucose deprivation-induced cellular injury in adult hippocampus. Neuropharmacology. 2004 Aug;47(2):253–62.
Pond, Brooks B., et al. “Chloride transport inhibitors influence recovery from oxygen-glucose deprivation-induced cellular injury in adult hippocampus.Neuropharmacology, vol. 47, no. 2, Aug. 2004, pp. 253–62. Pubmed, doi:10.1016/j.neuropharm.2004.04.002.
Pond BB, Galeffi F, Ahrens R, Schwartz-Bloom RD. Chloride transport inhibitors influence recovery from oxygen-glucose deprivation-induced cellular injury in adult hippocampus. Neuropharmacology. 2004 Aug;47(2):253–262.
Journal cover image

Published In

Neuropharmacology

DOI

ISSN

0028-3908

Publication Date

August 2004

Volume

47

Issue

2

Start / End Page

253 / 262

Location

England

Related Subject Headings

  • Solute Carrier Family 12, Member 2
  • Solute Carrier Family 12, Member 1
  • Sodium Potassium Chloride Symporter Inhibitors
  • Rats, Sprague-Dawley
  • Rats
  • Neurons
  • Neurology & Neurosurgery
  • Male
  • In Vitro Techniques
  • Hypoxia