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We previously showed that IL-6 has a neuroprotective effect.Herein, we explored mechanism underlying the IL-6 neuroprotection.Cerebellar granule neurons from postnatal 8-day infant rats were chronically exposed to IL-6 or JAK inhibitor AG490.DAN and 2-APB were used to antagonize ryanodine receptor (RyR)and inositol 1,4,5-trisphosphate receptor (IP3R), respectively.IL-6 prevented NMDA-evoked intracellular Ca2+overload and neuronal apoptosis and necrosis.AG490 blocked these IL-6 effects.