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Changes in intracellular chloride after oxygen-glucose deprivation of the adult hippocampal slice: effect of diazepam.

Publication ,  Journal Article
Galeffi, F; Sah, R; Pond, BB; George, A; Schwartz-Bloom, RD
Published in: J Neurosci
May 5, 2004

Ischemic injury to the CNS results in loss of ionic homeostasis and the development of neuronal death. An increase in intracellular Ca2+ is well established, but there are few studies of changes in intracellular Cl- ([Cl-]i) after ischemia. We used an in vitro model of cerebral ischemia (oxygen-glucose deprivation) to examine changes in [Cl-]i and GABA(A) receptor-mediated responses in hippocampal slices from adult rats. Changes in [Cl-]i were measured in area CA1 pyramidal neurons using optical imaging of 6-methoxy-N-ethylquinolinium chloride, a Cl--sensitive fluorescent indicator. Oxygen-glucose deprivation induced an immediate rise in [Cl-]i, which recovered within 20 min. A second and more prolonged rise in [Cl-]i occurred within the next hour, during which postsynaptic field potentials failed to recover. The sustained increase in [Cl-]i was not blocked by GABA(A) receptor antagonists. However, oxygen-glucose deprivation caused a progressive downregulation of the K+-Cl- cotransporter (KCC2), which may have contributed to the Cl- accumulation. The rise in [Cl-]i was accompanied by an inability of the GABA(A) agonist muscimol to cause Cl- influx. In vivo, diazepam is neuroprotective when given early after ischemia, although the mechanism by which this occurs is not well understood. Here, we added diazepam early after oxygen-glucose deprivation and prevented the downregulation of KCC2 and the accumulation of [Cl-]i. Consequently, both GABA(A) responses and synaptic transmission within the hippocampus were restored. Thus, after oxygen-glucose deprivation, diazepam may decrease neuronal excitability, thereby reducing the energy demands of the neuron. This may prevent the activation of downstream cell death mechanisms and restore Cl- homeostasis and neuronal function

Duke Scholars

Published In

J Neurosci

DOI

EISSN

1529-2401

Publication Date

May 5, 2004

Volume

24

Issue

18

Start / End Page

4478 / 4488

Location

United States

Related Subject Headings

  • Synaptic Transmission
  • Symporters
  • Solute Carrier Family 12, Member 2
  • Sodium-Potassium-Chloride Symporters
  • Recovery of Function
  • Receptors, GABA-A
  • Rats, Sprague-Dawley
  • Rats
  • Quinolinium Compounds
  • Neuroprotective Agents
 

Citation

APA
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ICMJE
MLA
NLM
Galeffi, F., Sah, R., Pond, B. B., George, A., & Schwartz-Bloom, R. D. (2004). Changes in intracellular chloride after oxygen-glucose deprivation of the adult hippocampal slice: effect of diazepam. J Neurosci, 24(18), 4478–4488. https://doi.org/10.1523/JNEUROSCI.0755-04.2004
Galeffi, Francesca, Renu Sah, Brooks B. Pond, Amanda George, and Rochelle D. Schwartz-Bloom. “Changes in intracellular chloride after oxygen-glucose deprivation of the adult hippocampal slice: effect of diazepam.J Neurosci 24, no. 18 (May 5, 2004): 4478–88. https://doi.org/10.1523/JNEUROSCI.0755-04.2004.
Galeffi F, Sah R, Pond BB, George A, Schwartz-Bloom RD. Changes in intracellular chloride after oxygen-glucose deprivation of the adult hippocampal slice: effect of diazepam. J Neurosci. 2004 May 5;24(18):4478–88.
Galeffi, Francesca, et al. “Changes in intracellular chloride after oxygen-glucose deprivation of the adult hippocampal slice: effect of diazepam.J Neurosci, vol. 24, no. 18, May 2004, pp. 4478–88. Pubmed, doi:10.1523/JNEUROSCI.0755-04.2004.
Galeffi F, Sah R, Pond BB, George A, Schwartz-Bloom RD. Changes in intracellular chloride after oxygen-glucose deprivation of the adult hippocampal slice: effect of diazepam. J Neurosci. 2004 May 5;24(18):4478–4488.

Published In

J Neurosci

DOI

EISSN

1529-2401

Publication Date

May 5, 2004

Volume

24

Issue

18

Start / End Page

4478 / 4488

Location

United States

Related Subject Headings

  • Synaptic Transmission
  • Symporters
  • Solute Carrier Family 12, Member 2
  • Sodium-Potassium-Chloride Symporters
  • Recovery of Function
  • Receptors, GABA-A
  • Rats, Sprague-Dawley
  • Rats
  • Quinolinium Compounds
  • Neuroprotective Agents