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Tetramethylpyrazine nitrone, a multifunctional neuroprotective agent for ischemic stroke therapy
Zhang Z.4; Zhang G.4; Sun Y.4; Szeto S.S.W.3; Law H.C.H.3; Quan Q.3; Li G.3; Yu P.4; Sho E.1; Siu M.K.W.2; Lee S.M.Y.5; Chu I.K.3; Wang Y.4
2016-11-14
Source PublicationScientific Reports
ISSN20452322
Volume6
AbstractTBN, 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
Language英語
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Cited Times [WOS]:8   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
Affiliation1.National Engineering Research Center of Biomedicine and Animal Science
2.University of Windsor
3.The University of Hong Kong
4.Jinan University
5.University of Macau
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GB/T 7714
Zhang Z.,Zhang G.,Sun Y.,et al. Tetramethylpyrazine nitrone, a multifunctional neuroprotective agent for ischemic stroke therapy[J]. Scientific Reports,2016,6.
APA Zhang Z..,Zhang G..,Sun Y..,Szeto S.S.W..,Law H.C.H..,...&Wang Y..(2016).Tetramethylpyrazine nitrone, a multifunctional neuroprotective agent for ischemic stroke therapy.Scientific Reports,6.
MLA Zhang Z.,et al."Tetramethylpyrazine nitrone, a multifunctional neuroprotective agent for ischemic stroke therapy".Scientific Reports 6(2016).
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