NADPH is superior to NADH or edaravone in ameliorating metabolic disturbance and brain injury in ischemic stroke

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.

Targeting Molecular Mediators of Ferroptosis and Oxidative Stress for Neurological Disorders

“…It participates in a variety of biochemical reactions as a hydrogen transmitter in vivo. Studies have confirmed that NADPH can resist oxidative stress and improve energy metabolism, so as to play a neuroprotective role in stroke [146]. NADPH oxidases (NOXs) have 7 kinds of subtypes.…”

Regulation of FSP1 myristoylation by NADPH: A novel mechanism for ferroptosis inhibition

“…Surprisingly, we have previously found that i.v. NADPH can be well enriched in the brain and has dramatic therapeutic efficacy against ischemic encephalopathy [ 55 ]. There is a widespread belief that NADP + or NADPH must be generated by intracellular metabolism and cannot be transported from the extracellular space [ 25 ].…”

Monocyte, Neutrophil and Whole Blood Transcriptome Dynamics Following Ischemic Stroke

“…There were exceptions, such as the “Regulation of Golgi to plasma membrane protein transport” pathway, which progressively decreased in expression in monocytes in CE, LV and SV stroke, a pathway shown to affect outcomes in experimental stroke [119]. Another example was “NADH oxidation” which peaked at 24 h in neutrophils in CE, LV and SV strokes and is known to play a role in experimental stroke [120]. There were few shared GO terms enriched in DEGs in whole blood CE, LV and SV strokes, likely related to the cellular heterogeneity of whole blood.…”