Author | Search for: Tauskela, Joseph S.1; Search for: Mealing, Geoff1; Search for: Comas, Tanya1; Search for: Brunette, Eric1; Search for: Monette, Robert1; Search for: Small, Daniel L.1; Search for: Morley, Paul1 |
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Affiliation | - National Research Council of Canada. NRC Institute for Biological Sciences
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Format | Text, Article |
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Subject | 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid; 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid; acid; anaerobiosis; calcium; Canada; cell survival; cells, cultured; cerebral cortex; cytology; dose-response relationship, drug; drug effects; female; glucose; glutamic acid; membrane potentials; metabolism; N-methylaspartate; neurons; oxygen; pharmacology; physiology; pregnancy; protection; rats; rats, sprague-dawley; receptor; support, Non-U. S. Gov't; toxicity |
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Abstract | The Cl(-) channel blockers, 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) or 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid (SITS) dose-dependently protected against oxygen-glucose deprivation in cultured rat cortical neurons. DIDS or SITS attenuated oxygen-glucose deprivation-induced increases in extracellular glutamate concentrations and intracellular Ca(2+). DIDS or SITS provided moderate protection against N-methyl-D-aspartate (NMDA) toxicity and decreased NMDA receptor-mediated increases in intracellular Ca(2+). Whole-cell NMDA receptor currents were attenuated 39+/-2% and 21+/-3% by 1 mM DIDS and SITS, respectively. Other Cl(-) channel blockers as equipotent as DIDS and SITS did not decrease oxygen-glucose deprivation- or NMDA-mediated neuronal Ca(2+) influx or toxicity. Neurotoxicity by exogenous glutamate was not prevented by SITS and was exacerbated by DIDS. Reductions in oxygen-glucose deprivation-induced increases in intracellular Ca(2+) levels underlie neuroprotection by DIDS and SITS. This was a reflection of lower extracellular [glutamate], direct inhibition of Ca(2+) influx through postsynaptic NMDA receptors, and possibly through other protective properties associated with DIDS and SITS |
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Publication date | 2003-03-07 |
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In | |
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Language | English |
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NRC number | TAUSKELA2003A |
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NPARC number | 9382806 |
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Export citation | Export as RIS |
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Record identifier | 43a21616-c017-456d-b5fe-6ae04b5a2e81 |
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Record created | 2009-07-10 |
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Record modified | 2020-04-02 |
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