Contribution of Zinc-Dependent Delayed Calcium Influx via TRPC5 in Oxidative Neuronal Death and its Prevention by Novel TRPC Antagonist.
MixedOtherSprague Dawley (in vivo); ICR and 129S1/SvImJ TRPC5 knockout mice (in vitro)Male (in vivo); both sexes (cultures)n = At least eight male animals per in vivo experimentIntraperitoneal100 micrograms/kg in vivo; 10 micromolar in vitro30 min after kainate injection
Model: Kainate-induced prolonged seizures, 10 mg/kg kainate intraperitoneally, terminated at 2.5 h with 50 mg/kg sodium phenytoin; in vitro hydrogen peroxide oxidative neuronal injury
NU6027 given 30 min after kainate reduced 24 h mortality from 38 per cent to zero and significantly reduced Fluoro-Jade B positive dead neurons in hippocampal CA1 and CA3, without altering seizure severity or body weight loss. TRPC5 knockout cortical neurons were resistant to hydrogen peroxide indu…
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