Combination of NAD+ and NADPH Offers Greater Neuroprotection in Ischemic Stroke Models by Relieving Metabolic Stress

Qiao Huang, Meiling Sun, Mei Li, Dingmei Zhang, Feng Han, Jun Chao Wu, Kohji Fukunaga, Zhong Chen, Zheng Hong Qin

Research output: Contribution to journalArticlepeer-review

38 Citations (Scopus)


Both reduced nicotinamide adenine dinucleotide phosphate (NADPH) and β-nicotinamide adenine dinucleotide hydrate (NAD+) have been reported to have potent neuroprotective effects against ischemic neuronal injury. Both NADPH and NAD+ are essential cofactors for anti-oxidation and cellular energy metabolism. We investigated if combined NADPH and NAD+ could offer better neuroprotective effects on cellular and animal models of ischemic stroke. In vitro studies with primary cultured neurons demonstrated that NAD+ was effective in protecting neurons against oxygen–glucose deprivation/reoxygenation (OGD/R) injury when given during the early time period of reoxygenation. In vivo studies in mice also suggested that NAD+ was effective for ameliorating ischemic brain damage when administered within 2 h after reperfusion. The combination of NADPH and NAD+ provided not only greater beneficial effects but also larger therapeutic window in both cellular and animal models of stroke. The combination of NADPH and NAD+ significantly increased the levels of adenosine triphosphate (ATP) and reduced the levels of reactive oxygen species (ROS) and oxidative damage of macromolecules. Furthermore, the combined medication significantly reduced long-term mortality, improved the functional recovery, and inhibited signaling pathways involved in apoptosis and necroptosis after ischemic stroke. The present study indicates that the combination of NAD+ and NADPH can produce greater therapeutic effects with smaller dose of NADPH; on the other hand, NADPH can significantly prolong the therapeutic window of NAD+. The current results suggest that the combination of NADPH and NAD+ may provide a novel effective therapy for ischemic stroke.

Original languageEnglish
Pages (from-to)6063-6075
Number of pages13
JournalMolecular Neurobiology
Issue number7
Publication statusPublished - 2018 Jul 1


  • Apoptosis
  • NAD
  • ROS
  • Stroke

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience


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