Mechanisms of dantrolene‐induced neuroprotection against excitotoxic injury

Abstract

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.