Statin-mediated neuroprotection is concentration and time dependent. A, Statins potently protect neurons from NMDA excitotoxicity, consistent with inhibition of HMG-CoA reductase. Cortical cultures were treated with various concentrations of the indicated statins for 6 d before NMDA exposure. *, p < 0.05 vs rosuvastatin; ‡, p < 0.01 vs rosuvastatin. B, Statin-induced neuroprotection developed over several days of pretreatment. Cortical cultures were exposed to either 100 nm simvastatin or 300 nm mevastatin for the indicated number of days before NMDA exposure.