N-acetylcysteine amide confers neuroprotection, improves bioenergetics and behavioral outcome following TBI.
N-acetylcysteine amide confers neuroprotection, improves bioenergetics and behavioral outcome following TBI.
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DOI：
10.1016/j.expneurol.2014.04.020
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发表时间：
2014-07
影响因子：
5.3
通讯作者：
Sullivan, Patrick G.
中科院分区：
文献类型：
--
作者：
Pandya, Jignesh D.;Readnower, Ryan D.;Patel, Samir P.;Yonutas, Heather M.;Pauly, James R.;Goldstein, Glenn A.;Rabchevsky, Alexander G.;Sullivan, Patrick G.
创伤性脑损伤（TBI）已成为一种日益增长的流行病，但尚未确定批准的药物治疗。我们以前的工作表明，线粒体氧化应激/损伤和生物能量损失在实验性TBI后神经元细胞死亡和行为结果中起着关键作用。一种已经取得一些实验成功的策略是使用其前体N-乙酰半胱氨酸（NAC）靶向谷胱甘肽。然而，这种方法受到NAC的低CNS生物利用度的阻碍。目前的研究评估了一种新的，细胞渗透性酰胺形式的N-乙酰半胱氨酸（NACA），它具有高渗透性，通过细胞和线粒体膜，导致增加中枢神经系统的生物利用度。在TBI后用NACA、NAC或载体处理的大鼠中评估皮质组织保留、认知功能和氧化应激标志物。在损伤后15天，与NAC或媒介物治疗的动物相比，用NACA治疗的动物表现出认知功能和皮质组织保留的显著改善。NACA治疗还显示在损伤后7天减少氧化损伤（HNE水平）。从机制上讲，损伤后NACA给药被证明可维持与假手术动物相当的线粒体谷胱甘肽和线粒体生物能量学水平。总的来说，这些数据提供了一个基本的平台，考虑NACA作为一种新的治疗剂治疗TBI。
Traumatic brain injury (TBI) has become a growing epidemic but no approved pharmacological treatment has been identified. Our previous work indicates that mitochondrial oxidative stress/damage and loss of bioenergetics play a pivotal role in neuronal cell death and behavioral outcome following experimental TBI. One tactic that has had some experimental success is to target glutathione using its precursor N-acetylcysteine (NAC). However, this approach has been hindered by the low CNS bioavailability of NAC. The current study evaluated a novel, cell permeant amide form of N-acetylcysteine (NACA), which has high permeability through cellular and mitochondrial membranes resulting in increased CNS bioavailability. Cortical tissue sparing, cognitive function and oxidative stress markers were assessed in rats treated with NACA, NAC, or vehicle following a TBI. At 15 days post-injury, animals treated with NACA demonstrated significant improvements in cognitive function and cortical tissue sparing compared to NAC or vehicle treated animals. NACA treatment also was shown to reduce oxidative damage (HNE levels) at 7 days post-injury. Mechanistically, post-injury NACA administration was demonstrated to maintain levels of mitochondrial glutathione and mitochondrial bioenergetics comparable to sham animals. Collectively these data provide a basic platform to consider NACA as a novel therapeutic agent for treatment of TBI.
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大鼠创伤性脑损伤后对脑炎症反应的抑制作用：N-乙酰半胱氨酸的潜在神经保护机制。
影响因子：
4.6
作者：
Chen, Gang;Shi, Jixin;Hu, Zhigang;Hang, Chunhua
通讯作者：
Hang, Chunhua
影响因子：
4.2
作者：
Davis, Laurie M.;Pauly, James R.;Sullivan, Patrick G.
通讯作者：
Sullivan, Patrick G.
影响因子：
4.2
作者：
Hall, Edward D.;Bryant, Ying Deng;Sullivan, Patrick G.
通讯作者：
Sullivan, Patrick G.
DOI：
10.3389/fnene.2013.00010
发表时间：
2013-01-01
期刊：
Frontiers in neuroenergetics
影响因子：
--
作者：
Pandya, Jignesh D;Nukala, Vidya N;Sullivan, Patrick G
通讯作者：
Sullivan, Patrick G
影响因子：
9.2
作者：
Avery, Michelle A;Rooney, Timothy M;Pandya, Jignesh D;Wishart, Thomas M;Gillingwater, Thomas H;Geddes, James W;Sullivan, Patrick G;Freeman, Marc R
通讯作者：
Freeman, Marc R