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• W2140322259 abstract "Ischemic injury to the CNS results in loss of ionic homeostasis and the development of neuronal death. An increase in intracellular Ca 2+ 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." @default.
• W2140322259 created "2016-06-24" @default.
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• W2140322259 date "2004-05-05" @default.
• W2140322259 modified "2023-10-01" @default.
• W2140322259 title "Changes in Intracellular Chloride after Oxygen–Glucose Deprivation of the Adult Hippocampal Slice: Effect of Diazepam" @default.
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• W2140322259 doi "https://doi.org/10.1523/jneurosci.0755-04.2004" @default.
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