Journal of Cerebral Blood Flow & Metabolism

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The NAD+ Precursor Nicotinamide Governs Neuronal Survival During Oxidative Stress Through Protein Kinase B Coupled to FOXO3a and Mitochondrial Membrane Potential

Zhao Zhong Chong, Shi-Hua Lin and Kenneth Maiese

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Figure 1.

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Nicotinamide (NIC) increases neuronal survival after oxidative stress in a concentration specific manner. (A) Increasing concentrations of NIC (1 to 50 mmol/L) were applied to neuronal cultures for a 24-hour period. Neuronal survival in the presence of NIC at the concentrations of 5 to 25 mmol/L was not significantly different from the cultures in the absence of NIC. Neuronal toxicity of NIC was present only in the cultures with 50 mmol/L of NIC (*P < 0.01 vs. untreated control [Con] cultures). (B) Primary hippocampal neurons were exposed to OGD for a period of 1, 2, 3, and 4 hours and neuronal survival was determined 24 hours after OGD. Neuronal survival was progressively decreased over a 4-hour period of OGD exposure (*P < 0.01 vs. untreated control). (C) Neuronal cultures were pretreated with NIC 1 hour before a 3-hour period of OGD and cell survival was assessed 24 hours later. Protection of NIC against OGD was evident in cultures with 5 to 25 mmol/L NIC when compared with cultures exposed to OGD alone (*P < 0.01 vs. OGD). Con, untreated control cultures. (D) Protection of NIC was evident in posttreatment paradigms during OGD toxicity. Neurons were treated with 12.5 mmol/L NIC at 2, 4, 6, and 12 hours after a 3-hour period of OGD exposure and cell survival was assessed 24 hours later. Posttreatment with NIC at 2 and 4 hours after OGD increased neuronal survival significantly (*P < 0.01 vs. OGD).

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