Neuroprotective interaction produced by xenon and dexmedetomidine on in vitro and in vivo neuronal injury models
Neuroprotective interaction produced by xenon and dexmedetomidine on in vitro and in vivo neuronal injury models
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DOI：
10.1016/j.neulet.2006.09.020
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发表时间：
2006-12-01
影响因子：
2.5
通讯作者：
Maze, Mervyn
中科院分区：
文献类型：
--
作者：
Rajakumaraswamy, Nishanthan;Ma, Daqing;Maze, Mervyn
Xenon（一种NMDA受体拮抗剂）和dexmedetomidine（Dex）（一种α（2）-肾上腺素受体激动剂）均表现出神经保护作用。我们研究了它们相互作用的性质。体外：将来自新生小鼠的神经元和神经胶质细胞的原代共培养物暴露于氧和葡萄糖剥夺（OGD），并通过乳酸脱氢酶（LDH）的释放来评估所产生的神经元损伤。在体内：出生后7天的大鼠进行右颈总动脉结扎，然后缺氧90分钟。梗死面积在损伤后4天通过形态学标准进行评估。在伤后30天通过测试旋转棒上的协调性来评估长期神经功能。氙和地塞米松均以浓度依赖性方式降低LDH释放，IC 50值分别为42%atm（95%CI：35-52）和0.10 μ M（95%CI：0.08-0.16）。等辐射线分析表明，氙和地塞米松在体外联合作用是相加的。在体内，氙和地塞米松的组合，在单独不具有神经保护作用的剂量下，产生了显著的神经保护作用，如通过梗死面积的减少所测量的。长期神经功能数据证实了这些形态学数据。我们的研究表明，氙和地塞米松的组合提供了体外和体内协同的神经保护作用。(c)2006爱思唯尔爱尔兰有限公司保留所有权利。
Xenon, an NMDA receptor antagonist and dexmedetomidine (Dex), an alpha(2)-adrenoceptor agonist, both exhibit neuroprotective effects. We investigated the nature of their interaction. In vitro: a primary co-culture of neuronal and glial cells derived from neonatal mice was exposed to oxygen and glucose deprivation (OGD) and the resulting neuronal injury was assessed by the release of lactate dehydrogenase (LDH). In vivo: Postnatal rats aged 7 days underwent right common carotid artery ligation followed by 90 min of hypoxia. The area of infarction was assessed at four days post-injury by morphological criteria. Long-term neurological function was evaluated at 30 days post-injury by testing co-ordination on rotarod. Both xenon and Dex concentration-dependently reduced LDH release with IC50 values of 42% atm (95% CI: 35-52) and 0.10 mu M (95% CI: 0.08-0.16), respectively. Isobolographic analysis showed that combined effect of xenon and Dex in vitro was additive. In vivo, a combination of xenon and Dex, at doses that are individually not neuroprotective, produced significant neuroprotective effect as measured by reduction in area of infarction. The long-term neurological function data corroborated these morphological data. Our study demonstrates that the combination of xenon and Dex offers neuroprotection additively in vitro and synergistically in vivo. (c) 2006 Elsevier Ireland Ltd. All rights reserved.