| Objective: It has been suggested that auditory central nervous system is highly sensitiveto bilirubin,so the impairment of auditory function is the most consistent symptomsrelated to BE. To date, effective drug treatment to limit the neuronal damage in suchinfants is not available. Glutamate-mediated excitotoxicity has been proposed to be animportant contributing factor of bilirubin-induced neuronal toxicity. Riluzole is aprescription drug well-known for its increasing therapeutic use in treating neurologicaldisorders associated with glutamate excitotoxicity. In this study, we investigated whetherbilirubin induced hyperexcitation and excitotoxicity of VCN neurons could be inhibited byriluzole, and the underlying mechanism.Methods: Isolated VCN neurons were obtained from Sprague Dawley (SD) rats (12-15days old).The effect of riluzole on neuronal activity and bilirubin-induced neuronalhyperexcitability was recorded using gramicidin perforated patch-clamp technique. Afterthe fluorescent calcium indicator Rhod-2-AM staining, dissociated neurons were placedon a laser scanning confocal microscope for cytosolic Ca2+measurements.Apoptotic andnecrotic cells of cultured VCN neurons with Hoechst-PI staining were counted under theconfocal microscope to assess apoptosis and necrosis.Results: riluzole decreased the frequency of sEPSCs and spontaneous action potentialsin VCN neurons without influencing the amplitude of sEPSCs or exogenousglutamate-activated postsynaptic currents. Applying before or after bilirubin treatment,riluzole suppressed sEPSCs and action potentials potentiation, prevented Ca2+overload and cell death caused by bilirubin in neurons in the VCN.Conclusions: riluzole can inhibit neuronal hyperexcitation and excitotoxicity caused bybilirubin through suppressing presynaptic glutamate release and subsequent Ca2+overloadeffectively in the VCN neurons. These effects make riluzole a promising drug for treatingand preventing bilirubin-induced hearing disorder in infants. |
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