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Tetramethylpyrazine nitrone, a multifunctional neuroprotective agent for ischemic stroke therapy
Zaijun Zhang4; Gaoxiao Zhang4; Yewei Sun4; Samuel S. W. Szeto3; Henry C. H. Law3; Quan Quan3; Guohui Li3; Pei Yu4; Eiketsu Sho1; Michael K. W. Siu2; Simon M. Y. Lee5; Ivan K. Chu3; Yuqiang Wang4
2016-11-14
Source PublicationScientific Reports
ISSN20452322
Volume6
Abstract

TBN, a novel tetramethylpyrazine derivative armed with a powerful free radical-scavenging nitrone moiety, has been reported to reduce cerebral infarction in rats through multi-functional mechanisms of action. Here we study the therapeutic effects of TBN on non-human primate model of stroke. Thirty male Cynomolgus macaques were subjected to stroke with 4 hours ischemia and then reperfusion. TBN were injected intravenously at 3 or 6 hours after the onset of ischemia. Cerebral infarction was examined by magnetic resonance imaging at 1 and 4 weeks post ischemia. Neurological severity scores were evaluated during 4 weeks observation. At the end of experiment, protein markers associated with the stroke injury and TBN treatment were screened by quantitative proteomics. We found that TBN readily penetrated the blood brain barrier and reached effective therapeutic concentration after intravenous administration. It significantly reduced brain infarction and modestly preserved the neurological function of stroke-affected arm. TBN suppressed over-expression of neuroinflammatory marker vimentin and decreased the numbers of GFAP-positive cells, while reversed down-regulation of myelination-associated protein 2′, 3′-cyclic-nucleotide 3′-phosphodiesterase and increased the numbers of NeuN-positive cells in the ipsilateral peri-infarct area. TBN may serve as a promising new clinical candidate for the treatment of ischemic stroke.

DOI10.1038/srep37148
URLView the original
Indexed BySCIE
Language英语
WOS Research AreaScience & Technology - Other Topics
WOS SubjectMultidisciplinary Sciences
WOS IDWOS:000387853600001
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Cited Times [WOS]:11   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Affiliation1.Kunming Biomed International and National Engineering Research Center of Biomedicine and Animal Science, Kunming, 650500, China
2.Department of Chemistry and Biochemistry, University of Windsor, Windsor, Ontario, Canada
3.Department of Chemistry, the University of Hong Kong, Hong Kong, China
4.Institute of New Drug Research and Guangzhou Key Laboratory of Innovative Chemical Drug Research in Cardio-cerebrovascular Diseases, Jinan University College of Pharmacy, Guangzhou, 510632, China
5.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China
Recommended Citation
GB/T 7714
Zaijun Zhang,Gaoxiao Zhang,Yewei Sun,et al. Tetramethylpyrazine nitrone, a multifunctional neuroprotective agent for ischemic stroke therapy[J]. Scientific Reports,2016,6.
APA Zaijun Zhang.,Gaoxiao Zhang.,Yewei Sun.,Samuel S. W. Szeto.,Henry C. H. Law.,...&Yuqiang Wang.(2016).Tetramethylpyrazine nitrone, a multifunctional neuroprotective agent for ischemic stroke therapy.Scientific Reports,6.
MLA Zaijun Zhang,et al."Tetramethylpyrazine nitrone, a multifunctional neuroprotective agent for ischemic stroke therapy".Scientific Reports 6(2016).
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