Neuroprotection against excitotoxic and ischemic insults by bis(12)-hupyridone, a novel anti-acetylcholinesterase dimer, possibly via acting on multiple targets
文献类型：期刊论文
| 作者 | Zhao, YM; Dou, J; Luo, JL; Li, WM; Chan, HHN; Cui, W; Zhang, H; Han, RW; Carlier, PR; Zhang, XJ |
| 刊名 | BRAIN RESEARCH
 |
| 出版日期 | 2011 |
| 卷号 | 1421期号:1页码:100-109 |
| 关键词 | Bis(12)-hupyridone NMDA receptor Ischemia Stroke Neuroprotectant |
| 通讯作者 | Han, YF (reprint author), Hong Kong Polytech Univ, Inst Modern Med, Dept Appl Biol & Chem Technol, Hong Kong, Hong Kong, Peoples R China.,bcyfhan@polyu.edu.hk |
| 英文摘要 | The activation of N-methyl-D-aspartate (NMDA) receptors by excessive release of glutamate is involved in the pathogenesis of ischemic stroke. Thus the NMDA receptor has become an attractive therapeutic target for the development of neuroprotectants, especially from antagonists with moderate to low affinity. In the current study, NMDA receptor blockage and neuroprotective effects of bis(12)-hupyridone (B12H), a novel dimeric acetylcholinesterase inhibitor derived from a naturally occurring monomeric analog huperzine A, were investigated in vitro and in vivo. In primary rat cerebellar granule neurons, B12H (0.1 nM to 1 mu M) prevented glutamate-induced apoptosis in a concentration- and time-dependent manner. Receptor-ligand binding analysis showed that B12H competed with [(3)H]MK801 with a K(i) value of 7.7 mu M. In the 2-hour middle cerebral artery occlusion rat model, B12H (0.4 and 0.8 mg/kg, 30 min before-ischemia and 15 min post-ischemia, i.p.) significantly attenuated ischemia-induced apoptosis in the penumbra region, improved neurological behavior impairment, and decreased cerebral infarct volume, cerebral edema and neuronal apoptosis in the stroke model. Together, these results showed that B12H moderately blocks NMDA receptors at MK801 site and exerts neuroprotection against excitotoxic and ischemic insults in vitro and in vivo. Combined with our previous publications, we conjecture that B12H might exert neuroprotection via acting on multiple targets. (C) 2011 Elsevier B.V. All rights reserved. |
| 学科主题 | Neurosciences & Neurology |
| 类目[WOS] | Neurosciences |
| 关键词[WOS] | NMDA RECEPTOR ANTAGONIST ; FOCAL CEREBRAL-ISCHEMIA ; D-ASPARTATE RECEPTORS ; ALZHEIMERS-DISEASE ; HUPERZINE-A ; PARADIGM SHIFT ; BRAIN-DAMAGE ; MEMANTINE ; BIS(7)-TACRINE ; INHIBITION |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000297487400011 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/909]  |
| 专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
| 推荐引用方式 GB/T 7714 | Zhao, YM,Dou, J,Luo, JL,et al. Neuroprotection against excitotoxic and ischemic insults by bis(12)-hupyridone, a novel anti-acetylcholinesterase dimer, possibly via acting on multiple targets[J]. BRAIN RESEARCH,2011,1421(1):100-109. |
| APA | Zhao, YM.,Dou, J.,Luo, JL.,Li, WM.,Chan, HHN.,...&Han, YF.(2011).Neuroprotection against excitotoxic and ischemic insults by bis(12)-hupyridone, a novel anti-acetylcholinesterase dimer, possibly via acting on multiple targets.BRAIN RESEARCH,1421(1),100-109. |
| MLA | Zhao, YM,et al."Neuroprotection against excitotoxic and ischemic insults by bis(12)-hupyridone, a novel anti-acetylcholinesterase dimer, possibly via acting on multiple targets".BRAIN RESEARCH 1421.1(2011):100-109. |
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