Neuroprotective and Neuroregenerative Effects of Nimodipine in a Model System of Neuronal Differentiation and Neurite Outgrowth

Nimodipine is a Ca(2+)-channel antagonist mainly used for the management of aneurysmal subarachnoid hemorrhage (aSAH) to prevent cerebral vasospasms. However, it is not clear if the better outcome of nimodipine-treated patients is mainly due to vasodilatation or whether other cellular neuroprotective or neuregenerative effects of nimodipine are involved. We analysed PC12 cells after different stress stimuli with or without nimodipine pretreatment. Cytotoxicity of 200 mM EtOH and osmotic stress (450 mosmol/L) was significantly reduced with nimodipine pretreatment, while nimodipine has no influence on the hypoxia-induced cytotoxicity in PC12 cells. The presence of nimodipine also increased the NGF-induced neurite outgrowth in PC12 cells. However, nimodipine alone was not able to induce neurite outgrowth in PC12 cells. These results support the idea that nimodipine has general neuroprotective or neuregenerative effect beside its role in vasodilatation and is maybe useful also in other clinical applications beside aSAH.