Back to Search
Start Over
Combination of NAD+ and NADPH Offers Greater Neuroprotection in Ischemic Stroke Models by Relieving Metabolic Stress.
- Source :
- Molecular Neurobiology; Jul2018, Vol. 55 Issue 7, p6063-6075, 13p
- Publication Year :
- 2018
-
Abstract
- Both reduced nicotinamide adenine dinucleotide phosphate (NADPH) and β-nicotinamide adenine dinucleotide hydrate (NAD<superscript>+</superscript>) have been reported to have potent neuroprotective effects against ischemic neuronal injury. Both NADPH and NAD<superscript>+</superscript> are essential cofactors for anti-oxidation and cellular energy metabolism. We investigated if combined NADPH and NAD<superscript>+</superscript> could offer better neuroprotective effects on cellular and animal models of ischemic stroke. In vitro studies with primary cultured neurons demonstrated that NAD<superscript>+</superscript> 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<superscript>+</superscript> was effective for ameliorating ischemic brain damage when administered within 2 h after reperfusion. The combination of NADPH and NAD<superscript>+</superscript> 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<superscript>+</superscript> 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<superscript>+</superscript> 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<superscript>+</superscript>. The current results suggest that the combination of NADPH and NAD<superscript>+</superscript> may provide a novel effective therapy for ischemic stroke. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 08937648
- Volume :
- 55
- Issue :
- 7
- Database :
- Complementary Index
- Journal :
- Molecular Neurobiology
- Publication Type :
- Academic Journal
- Accession number :
- 130104164
- Full Text :
- https://doi.org/10.1007/s12035-017-0809-7