期刊
CNS NEUROSCIENCE & THERAPEUTICS
卷 22, 期 9, 页码 782-788出版社
WILEY-BLACKWELL
DOI: 10.1111/cns.12576
关键词
Aminopropyl carbazole chemical; Ischemic stroke; Neuroprotection; Nicotinamide adenine dinucleotide; Nicotinamide phosphoribosyltransferase; P7C3-A20
资金
- National Natural Science Foundation of China [81130061, 81373414, 81422049]
- National Science and Technology Major Project [2009ZX09303-002]
- National 863 Plan Young Scientist Program of China [2015AA020943]
AimNAMPT is a novel therapeutic target of ischemic stroke. The aim of this study was to investigate the effect of a potential NAMPT activator, P7C3-A20, an aminopropyl carbazole derivative, on ischemic stroke. MethodsIn vitro study, neuron protection effect of P7C3-A20 was investigated by co-incubation with primary neurons subjected to oxygen-glucose deprivation (OGD) or oxygen-glucose deprivation/reperfusion (OGD/R) injury. In vivo experiment, P7C3-A20 was administrated in middle cerebral artery occlusion (MCAO) rats and infarct volume was examined. Lastly, the brain tissue nicotinamide adenine dinucleotide (NAD) levels were detected in P7C3-A20 treated normal or MCAO mice. ResultsCell viability, morphology, and Tuj-1 staining confirmed the neuroprotective effect of P7C3-A20 in OGD or OGD/R model. P7C3-A20 administration significantly reduced cerebral infarction in MCAO rats. Moreover, brain NAD levels were elevated both in normal and MCAO mice after P7C3-A20 treatment. ConclusionsP7C3-A20 has neuroprotective effect in cerebral ischemia. The study contributes to the development of NAMPT activators against ischemic stroke and expands the horizon of the neuroprotective effect of aminopropyl carbazole chemicals.
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