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.

Xin-xin Wang;Fan Wang;Guang-hui Mao;Jun-chao Wu;Mei Li;Rong Han;Jing She;Rong Zhang;Rui Sheng;Zhong Chen;Zheng-hong Qin

Department of Pharmacology and Laboratory of Aging and Nervous Diseases,Jiangsu Key Laboratory of Neuropsychiatric Diseases,College of Pharmaceutical Sciences,Soochow University,Suzhou 215123,China;Institute of Pediatric Research,Children's Hospital of Soochow University,Suzhou 215025,China;College of Pharmaceutical Sciences,Zhejiang Chinese Medical University,Hangzhou 310053,China;Institute of Pharmacology and Toxicology,College of Pharmaceutical Sciences,Zhejiang University,Hangzhou 310058,China

中国药理学报（英文版）

[1]Xin-xin Wang;Fan Wang;Guang-hui Mao;Jun-chao Wu;Mei Li;Rong Han;Jing She;Rong Zhang;Rui Sheng;Zhong Chen;Zheng-hong Qin-.NADPH is superior to NADH or edaravone in ameliorating metabolic disturbance and brain injury in ischemic stroke)[J].中国药理学报（英文版）,2022(03):529-540

NADPH,superior,NADH,edaravone,ameliorating,metabolic,disturbance,brain,injury,ischemic,stroke,Our,previous,studies,confirm,that,exogenous,reduced,nicotinamide,adenine,dinucleotide,phosphate,exerts,neuroprotective,animal,models,its,primary,mechanism,related,oxidative,stress,improved,energy,metabolism,However,unknown,whether,also,plays,role,against,In,this,study,compared,efficacy,Transient,middle,cerebral,artery,occlusion,reperfusion,MCAO,mouse,vitro,glucose,deprivation,reoxygenation,OGD,were,established,mice,intravenously,administered,optimal,dose,immediately,after,We,showed,overall,was,had,longer,therapeutic,window,within,than,addition,better,alleviating,atrophy,while,increasing,survival,stronger,antioxidant,effects,but,best,terms,maintaining,Taken,together,demonstrates

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