Mechanisms of dantrolene‐induced neuroprotection against excitotoxic injury

Dantrolene – an inhibitor of ryanodine receptors and calcium stabilizer – prevents ischemia‐ and excitotoxicity‐evoked neurodegeneration. To elucidate the mechanisms of this phenomenon, we investigated effects of dantrolene on the NMDA‐ and glutamate‐induced lesion and stimulation of ⁴⁵Ca uptake in primary cultures of rat cerebellar granule neurons. Neurodegeneration was evaluated after 24 h with the propidium iodide staining. Bcl‐2 immunoreactivity in cell homogenates was measured by immunoblotting. The results demonstrated that dantrolene applied at micromolar concentrations inhibits in a dose‐dependent manner NMDA‐ and glutamate‐evoked ⁴⁵Ca uptake in neurones and induces neuroprotection. This effect was additive to known effects of DMSO, a vehicle to dantrolene. Dantrolene failed to induce changes in Bcl‐2 immunoreactivity. Thus, dantrolene‐induced neuroprotection against excitotoxicity may be at least partially mediated by its inhibitory effect on the NMDA receptors.