title: Reduced Nicotinamide Adenine Dinucleotide Phosphate, a Pentose Phosphate Pathway Product, Might Be a Novel Drug Candidate for Ischemic Stroke.
abstract: OBJECTIVE
  Our previous study has defined a role of TP53-induced glycolysis and apoptosis regulator in neuroprotection against ischemic injury through increasing the flow of pentose phosphate pathway. We hypothesized that the pentose phosphate pathway product nicotinamide adenine dinucleotide phosphate (NADPH) could be a novel drug for treatment of ischemic stroke.
  
  
  METHODS
  The NADPH was given before, at the onset, or after stroke onset with single or repeated intravenous (mice and rats) or intraperitoneal injections (monkey). The short- and long-term therapeutic effects of NADPH were evaluated in male adult ICR mice (total=614) with transient middle cerebral artery occlusion, in male adult Sprague-Dawley rats (total=114) with permanent middle cerebral artery occlusion, and in male adult rhesus monkey (total=12) with thrombotic middle cerebral artery occlusion.
  
  
  RESULTS
  Administration of NADPH led to a dramatic increase in the levels of ATP and reduced form of glutathione, whereas it decreased the levels of reactive oxygen species. NADPH significantly reduced infarct volume, improved poststroke survival, and recovery of neurological functions in mouse and rat models of stroke. Robust neuroprotection of a single dose of NADPH was seen when it was administered within 5 hours after reperfusion; however, repeat administration of NADPH twice a day for 7 days starting 24 hours after the onset of stroke also offered therapeutic effects. Pretreatment with NADPH also significantly improved the outcome of stroke insult.
  
  
  CONCLUSIONS
  Administration of exogenous NADPH significantly protected neurons against ischemia/reperfusion-induced injury in 2 rodent stroke models. Thus, NADPH might be a promising drug candidate for treatment of ischemic stroke.
authors.affiliation: From the Laboratory of Aging and Nervous Diseases, Department of Pharmacology, Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, College of Pharmaceutical Science, Soochow University, Suzhou, China (M.L., M.S., L.C., J.C., Y.-Y.Q., R.S., J.-C.W., Z.-H.Q.); Department of Radiology, Affiliated Hospital of Guilin Medical College, Guilin, China (Z.-P.Z.); Department of Pathophysiology, Nantong University School of Medicine, Nantong, China (J.-H.G.); Institute of Pharmacology and Toxicology, Zhejiang University School of Pharmaceutical Science, Hangzhou, China (F.H.); and Key Laboratory of Arrhythmias, Ministry of Education, East Hospital, Tongji University School of Medicine, Shanghai, China (Y.D.).
authors.forename: Mei
authors.initials: M
authors.lastname: Li
authors.affiliation: From the Laboratory of Aging and Nervous Diseases, Department of Pharmacology, Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, College of Pharmaceutical Science, Soochow University, Suzhou, China (M.L., M.S., L.C., J.C., Y.-Y.Q., R.S., J.-C.W., Z.-H.Q.); Department of Radiology, Affiliated Hospital of Guilin Medical College, Guilin, China (Z.-P.Z.); Department of Pathophysiology, Nantong University School of Medicine, Nantong, China (J.-H.G.); Institute of Pharmacology and Toxicology, Zhejiang University School of Pharmaceutical Science, Hangzhou, China (F.H.); and Key Laboratory of Arrhythmias, Ministry of Education, East Hospital, Tongji University School of Medicine, Shanghai, China (Y.D.).
authors.forename: Zhi-Peng
authors.initials: ZP
authors.lastname: Zhou
authors.affiliation: From the Laboratory of Aging and Nervous Diseases, Department of Pharmacology, Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, College of Pharmaceutical Science, Soochow University, Suzhou, China (M.L., M.S., L.C., J.C., Y.-Y.Q., R.S., J.-C.W., Z.-H.Q.); Department of Radiology, Affiliated Hospital of Guilin Medical College, Guilin, China (Z.-P.Z.); Department of Pathophysiology, Nantong University School of Medicine, Nantong, China (J.-H.G.); Institute of Pharmacology and Toxicology, Zhejiang University School of Pharmaceutical Science, Hangzhou, China (F.H.); and Key Laboratory of Arrhythmias, Ministry of Education, East Hospital, Tongji University School of Medicine, Shanghai, China (Y.D.).
authors.forename: Meiling
authors.initials: M
authors.lastname: Sun
authors.affiliation: From the Laboratory of Aging and Nervous Diseases, Department of Pharmacology, Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, College of Pharmaceutical Science, Soochow University, Suzhou, China (M.L., M.S., L.C., J.C., Y.-Y.Q., R.S., J.-C.W., Z.-H.Q.); Department of Radiology, Affiliated Hospital of Guilin Medical College, Guilin, China (Z.-P.Z.); Department of Pathophysiology, Nantong University School of Medicine, Nantong, China (J.-H.G.); Institute of Pharmacology and Toxicology, Zhejiang University School of Pharmaceutical Science, Hangzhou, China (F.H.); and Key Laboratory of Arrhythmias, Ministry of Education, East Hospital, Tongji University School of Medicine, Shanghai, China (Y.D.).
authors.forename: Lijuan
authors.initials: L
authors.lastname: Cao
authors.affiliation: From the Laboratory of Aging and Nervous Diseases, Department of Pharmacology, Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, College of Pharmaceutical Science, Soochow University, Suzhou, China (M.L., M.S., L.C., J.C., Y.-Y.Q., R.S., J.-C.W., Z.-H.Q.); Department of Radiology, Affiliated Hospital of Guilin Medical College, Guilin, China (Z.-P.Z.); Department of Pathophysiology, Nantong University School of Medicine, Nantong, China (J.-H.G.); Institute of Pharmacology and Toxicology, Zhejiang University School of Pharmaceutical Science, Hangzhou, China (F.H.); and Key Laboratory of Arrhythmias, Ministry of Education, East Hospital, Tongji University School of Medicine, Shanghai, China (Y.D.).
authors.forename: Jieyu
authors.initials: J
authors.lastname: Chen
authors.affiliation: From the Laboratory of Aging and Nervous Diseases, Department of Pharmacology, Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, College of Pharmaceutical Science, Soochow University, Suzhou, China (M.L., M.S., L.C., J.C., Y.-Y.Q., R.S., J.-C.W., Z.-H.Q.); Department of Radiology, Affiliated Hospital of Guilin Medical College, Guilin, China (Z.-P.Z.); Department of Pathophysiology, Nantong University School of Medicine, Nantong, China (J.-H.G.); Institute of Pharmacology and Toxicology, Zhejiang University School of Pharmaceutical Science, Hangzhou, China (F.H.); and Key Laboratory of Arrhythmias, Ministry of Education, East Hospital, Tongji University School of Medicine, Shanghai, China (Y.D.).
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Qin
authors.affiliation: From the Laboratory of Aging and Nervous Diseases, Department of Pharmacology, Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, College of Pharmaceutical Science, Soochow University, Suzhou, China (M.L., M.S., L.C., J.C., Y.-Y.Q., R.S., J.-C.W., Z.-H.Q.); Department of Radiology, Affiliated Hospital of Guilin Medical College, Guilin, China (Z.-P.Z.); Department of Pathophysiology, Nantong University School of Medicine, Nantong, China (J.-H.G.); Institute of Pharmacology and Toxicology, Zhejiang University School of Pharmaceutical Science, Hangzhou, China (F.H.); and Key Laboratory of Arrhythmias, Ministry of Education, East Hospital, Tongji University School of Medicine, Shanghai, China (Y.D.).
authors.forename: Jin-Hua
authors.initials: JH
authors.lastname: Gu
authors.affiliation: From the Laboratory of Aging and Nervous Diseases, Department of Pharmacology, Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, College of Pharmaceutical Science, Soochow University, Suzhou, China (M.L., M.S., L.C., J.C., Y.-Y.Q., R.S., J.-C.W., Z.-H.Q.); Department of Radiology, Affiliated Hospital of Guilin Medical College, Guilin, China (Z.-P.Z.); Department of Pathophysiology, Nantong University School of Medicine, Nantong, China (J.-H.G.); Institute of Pharmacology and Toxicology, Zhejiang University School of Pharmaceutical Science, Hangzhou, China (F.H.); and Key Laboratory of Arrhythmias, Ministry of Education, East Hospital, Tongji University School of Medicine, Shanghai, China (Y.D.).
authors.forename: Feng
authors.initials: F
authors.lastname: Han
authors.affiliation: From the Laboratory of Aging and Nervous Diseases, Department of Pharmacology, Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, College of Pharmaceutical Science, Soochow University, Suzhou, China (M.L., M.S., L.C., J.C., Y.-Y.Q., R.S., J.-C.W., Z.-H.Q.); Department of Radiology, Affiliated Hospital of Guilin Medical College, Guilin, China (Z.-P.Z.); Department of Pathophysiology, Nantong University School of Medicine, Nantong, China (J.-H.G.); Institute of Pharmacology and Toxicology, Zhejiang University School of Pharmaceutical Science, Hangzhou, China (F.H.); and Key Laboratory of Arrhythmias, Ministry of Education, East Hospital, Tongji University School of Medicine, Shanghai, China (Y.D.).
authors.forename: Rui
authors.initials: R
authors.lastname: Sheng
authors.affiliation: From the Laboratory of Aging and Nervous Diseases, Department of Pharmacology, Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, College of Pharmaceutical Science, Soochow University, Suzhou, China (M.L., M.S., L.C., J.C., Y.-Y.Q., R.S., J.-C.W., Z.-H.Q.); Department of Radiology, Affiliated Hospital of Guilin Medical College, Guilin, China (Z.-P.Z.); Department of Pathophysiology, Nantong University School of Medicine, Nantong, China (J.-H.G.); Institute of Pharmacology and Toxicology, Zhejiang University School of Pharmaceutical Science, Hangzhou, China (F.H.); and Key Laboratory of Arrhythmias, Ministry of Education, East Hospital, Tongji University School of Medicine, Shanghai, China (Y.D.).
authors.forename: Jun-Chao
authors.initials: JC
authors.lastname: Wu
authors.affiliation: From the Laboratory of Aging and Nervous Diseases, Department of Pharmacology, Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, College of Pharmaceutical Science, Soochow University, Suzhou, China (M.L., M.S., L.C., J.C., Y.-Y.Q., R.S., J.-C.W., Z.-H.Q.); Department of Radiology, Affiliated Hospital of Guilin Medical College, Guilin, China (Z.-P.Z.); Department of Pathophysiology, Nantong University School of Medicine, Nantong, China (J.-H.G.); Institute of Pharmacology and Toxicology, Zhejiang University School of Pharmaceutical Science, Hangzhou, China (F.H.); and Key Laboratory of Arrhythmias, Ministry of Education, East Hospital, Tongji University School of Medicine, Shanghai, China (Y.D.). qinzhenhong@suda.edu.cn dingyuqiang@gmail.com.
authors.forename: Yuqiang
authors.initials: Y
authors.lastname: Ding
authors.affiliation: From the Laboratory of Aging and Nervous Diseases, Department of Pharmacology, Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, College of Pharmaceutical Science, Soochow University, Suzhou, China (M.L., M.S., L.C., J.C., Y.-Y.Q., R.S., J.-C.W., Z.-H.Q.); Department of Radiology, Affiliated Hospital of Guilin Medical College, Guilin, China (Z.-P.Z.); Department of Pathophysiology, Nantong University School of Medicine, Nantong, China (J.-H.G.); Institute of Pharmacology and Toxicology, Zhejiang University School of Pharmaceutical Science, Hangzhou, China (F.H.); and Key Laboratory of Arrhythmias, Ministry of Education, East Hospital, Tongji University School of Medicine, Shanghai, China (Y.D.). qinzhenhong@suda.edu.cn dingyuqiang@gmail.com.
authors.forename: Zheng-Hong
authors.initials: ZH
authors.lastname: Qin
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology; D008253:Macaca mulatta; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009249:NADP / Q000008:administration & dosage*; D010427:Pentose Phosphate Pathway / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000188:drug therapy* / Q000473:pathology
chemical_list: D009249:NADP
keywords: NADPH; TIGAR protein, mouse; reactive oxygen species; reperfusion injury; stroke