Background And Purpose: Bilirubin encephalopathy as a result of hyperbilirubinemia is a devastating neurological disorder that occurs mostly in the neonatal period. To date, no effective drug treatment is available. Glutamate-mediated excitotoxicity is likely an important factor causing bilirubin encephalopathy. Thus, drugs suppressing the overrelease of glutamate may protect the brain against bilirubin excitotoxicity. Riluzole is a prescription drug known for its antiglutamatergic function. This study was conducted in the rat's ventral cochlear nucleus, a structure highly sensitive to bilirubin toxicity, to find whether riluzole can be used to inhibit bilirubin toxicity.

Experimental Approach: Electrophysiology changes were detected by perforated patch clamp technique. Calcium imaging using Rhod-2-AM as an indicator was used to study the intracellular calcium. Cell apoptosis and necrosis were measured by PI/Hoechst staining.

Key Results: In the absence of bilirubin, riluzole effectively decreased the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) and suppressed neuronal firing but did not change the amplitude of sEPSC and glutamate-activated currents (I(Glu)). Moreover, riluzole inhibited bilirubin-induced increases in the frequency of sEPSC and neuronal firing. Riluzole could prevent the bilirubin-induced increase in intracellular calcium, mediated by AMPA and NMDA receptors. Furthermore, riluzole significantly reduced bilirubin-induced cell death.

Conclusions And Implications: These data suggest that riluzole can protect neurons in the ventral cochlear nucleus from bilirubin-induced hyperexcitation and excitotoxicity through reducing presynaptic glutamate release.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6495421PMC
http://dx.doi.org/10.1111/cns.12355DOI Listing

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