Abstract
Our previous studies confirm that exogenous reduced nicotinamide adenine dinucleotide phosphate (NADPH) exerts a neuroprotective effect in animal models of ischemic stroke, and its primary mechanism is related to anti-oxidative stress and improved energy metabolism. However, it is unknown whether nicotinamide adenine dinucleotide (NADH) also plays a neuroprotective role and whether NADPH is superior to NADH against ischemic stroke? In this study we compared the efficacy of NADH, NADPH, and edaravone in ameliorating brain injury and metabolic stress in ischemic stroke. Transient middle cerebral artery occlusion/reperfusion (t-MCAO/R) mouse model and in vitro oxygen glucose deprivation/reoxygenation (OGD/R) model were established. The mice were intravenously administered the optimal dose of NADPH (7.5 mg/kg), NADH (22.5 mg/kg), or edaravone (3 mg/kg) immediately after reperfusion. We showed that the overall efficacy of NADPH in ameliorating ischemic injury was superior to NADH and edaravone. NADPH had a longer therapeutic time window (within 5 h) after reperfusion than NADH and edaravone (within 2 h) for ischemic stroke. In addition, NADPH and edaravone were better in alleviating the brain atrophy, while NADH and NADPH were better in increasing the long-term survival rate. NADPH showed stronger antioxidant effects than NADH and edaravone; but NADH was the best in terms of maintaining energy metabolism. Taken together, this study demonstrates that NADPH exerts better neuroprotective effects against ischemic stroke than NADH and edaravone.
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Acknowledgements
This work was supported by the National Natural Science Foundation of China (No. 81730092), the Natural Science Foundation of Jiangsu Province of China (BK20180207), Jiangsu Key Laboratory of Neuropsychiatric Diseases (BM2013003) and the Priority Academic Program Development of the Jiangsu Higher Education Institutes (PAPD).
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ZHQ contributed to the conception and design; XXW, FW, GHM, JCW, ML, RH, JS and RZ contributed to the acquisition of data or analysis and interpretation of data; XXW and FW drafted the paper; RS, ZC, and ZHQ supervised the experiments. All authors read and approved the final version to be published.
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Wang, Xx., Wang, F., Mao, Gh. et al. NADPH is superior to NADH or edaravone in ameliorating metabolic disturbance and brain injury in ischemic stroke. Acta Pharmacol Sin 43, 529–540 (2022). https://doi.org/10.1038/s41401-021-00705-5
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DOI: https://doi.org/10.1038/s41401-021-00705-5
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