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In this study, norepinephrine was tested in 0.1, 1, 10, 25 and 50 microM doses in 100 microM NMDA toxicity on cerebellar granular cell culture of rats. NMDA in 100 microM concentration induced cell death significantly with respect to controls. Death cell population was 1.08 +/- 0.44% in control and 22.15 +/- 2.46% in 100 microM NMDA (P0.0001). None of the norepinephrine concentrations administrated 15 min prior to NMDA was able to reduce death cell scores to control levels. Results were 8.75 +/- 0.83% in 0.1 microM, 7.0 +/- 1.01% in 1 microM, 17.25 +/- 1.31% in 10 microM, 35.5 +/- 1.38% in 25 microM and 17.9 +/- 1.72% in 50 microM norepinephrine plus 100 microM NMDA administrated groups (P0.0001 for all with respect to control). Labetalol, as an alpha and beta blocker in 0.5 microM concentration which was given 15 min prior to norepinephrine was able to block the effects of it. In comparison with 100 microM NMDA administered group, only low doses of norepinephrine reduced the death cell scores significantly (for 0.1 and 1 microM norepinephrine plus NMDA groups; P0.0001). For 10 and 50 microM norepinephrine plus NMDA groups, death cell scores were found statistically insignificant from the NMDA-administered group (P0.05 for both) while for the 25 microM norepinephrine plus NMDA group, the death cell score was found to be statistically increased (P0.0001).

The neuroprotective role of nimodipine was tested in kainic acid (50 and 100 microM) induced neurotoxicity in cerebellar granular cell cultures of 4 to 7 day-old rat pups. Nimodipine was applied in 50, 100 and 200 microM concentrations. Kainate, in either dose, induced cerebellar granular cell death in respect to controls and the results were statistically significant (P = 0.000 for both doses). However, kainic acid in 100 microM concentration led to higher rates of cell death than 50 microM (P = 0.017). The neuroprotective role of nimodipine in kainate induced neurotoxicity was dose dependent. Kainate toxicity in 50 microM concentration was blocked by 50 and 100 microM nimodipine concentrations (P = 0.006 and P = 0.002, respectively) while 200 microM nimodipine was found ineffective. The most effective nimodipine dose for 100 microM kainic acid neurotoxicity was 200 microM (P = 0.000) while 50 and 100 microM concentrations of nimodipine were found ineffective. In this study, we have proven the dose-dependent neuroprotective role of nimodipine in kainate induced neurotoxicity in cerebellar granular cell cultures of rat pups.