N-acetylcysteine amide preserves mitochondrial bioenergetics and improves functional recovery following spinal trauma.
N-acetylcysteine amide preserves mitochondrial bioenergetics and improves functional recovery following spinal trauma.
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DOI：
10.1016/j.expneurol.2014.04.026
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发表时间：
2014-07
影响因子：
5.3
通讯作者：
Rabchevsky, Alexander G.
中科院分区：
文献类型：
--
作者：
Patel, Samir P.;Sullivan, Patrick G.;Pandya, Jignesh D.;Goldstein, Glenn A.;VanRooyen, Jenna L.;Yonutas, Heather M.;Eldahan, Khalid C.;Morehouse, Johnny;Magnuson, David S. K.;Rabchevsky, Alexander G.
关键词：
线粒体功能障碍正成为挫伤性脊髓损伤（SCI）后神经保护策略的关键目标，并且维持线粒体功能的药理学化合物赋予神经保护并改善损伤后的长期后肢功能。在目前的研究中，我们评估了细胞渗透性硫醇，N-乙酰半胱氨酸酰胺（NACA），内源性抗氧化剂谷胱甘肽（GSH）的前体，急性线粒体功能的疗效，和长期的组织保护和后肢运动恢复后上腰椎挫伤SCI。一些指定的受伤成年雌性Sprague-Dawley大鼠（n=120）在损伤后15分钟和6小时接受溶媒或NACA（75、150、300或600 mg/kg）。24小时后，从单个1.5cm脊髓节段（以损伤部位为中心）分离总的、突触的和非突触的线粒体群体，并评估线粒体生物能量学。结果显示，急性SCI后受损的总线粒体生物能量学，NACA治疗以剂量依赖性方式显著改善，最大效果为300 mg/kg（n=4/组）。对于突触和非突触线粒体，仅300 mg/kg的NACA剂量显示出功效。相似剂量（300 mg/kg）也维持线粒体GSH接近正常水平。其他指定的损伤大鼠（n=21）在损伤后15分钟开始接受连续NACA（150或300 mg/kg/天）治疗一周，以评估损伤后6周的长期功能恢复。运动测试和新的步态分析显示，NACA显著改善了后肢功能，这与损伤部位的组织保留增加有关。总的来说，NACA治疗显着维持急性线粒体生物能学和正常的GSH水平SCI后，和延长交付导致显着的组织保护和改善后肢功能的恢复。
Mitochondrial dysfunction is becoming a pivotal target for neuroprotective strategies following contusion spinal cord injury (SCI) and the pharmacological compounds that maintain mitochondrial function confer neuroprotection and improve long-term hindlimb function after injury. In the current study we evaluated the efficacy of cell-permeating thiol, N-acetylcysteineamide (NACA), a precursor of endogenous antioxidant glutathione (GSH), on mitochondrial function acutely, and long-term tissue sparing and hindlimb locomotor recovery following upper lumbar contusion SCI. Some designated injured adult female Sprague-Dawley rats (n=120) received either Vehicle or NACA (75, 150, 300 or 600 mg/kg) at 15min and 6hrs post-injury. After 24hr the total, synaptic, and non-synaptic mitochondrial populations were isolated from a single 1.5cm spinal cord segment (centered at injury site) and assessed for mitochondrial bioenergetics. Results showed compromised total mitochondrial bioenergetics following acute SCI that was significantly improved with NACA treatment in a dose-dependent manner, with maximum effects at 300 mg/kg (n=4/group). For synaptic and non-synaptic mitochondria, only 300 mg/kg NACA dosage showed efficacy. Similar dosage (300mg/kg) also maintained mitochondrial GSH near normal levels. Other designated injured rats (n=21) received continuous NACA (150 or 300mg/kg/day) treatment starting at 15min post-injury for one week to assess long-term functional recovery over 6 weeks post-injury. Locomotor testing and novel gait analyses showed significantly improved hindlimb function with NACA that were associated with increased tissue sparing at the injury site. Overall, NACA treatment significantly maintained acute mitochondrial bioenergetics and normalized GSH levels following SCI, and prolonged delivery resulted in significant tissue sparing and improved recovery of hindlimb function.
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影响因子：
5.3
作者：
Kuerzi, J.;Brown, E. H.;Magnuson, D. S. K.
通讯作者：
Magnuson, D. S. K.
影响因子：
7.4
作者：
ARUOMA, OI;HALLIWELL, B;BUTLER, J
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BUTLER, J
影响因子：
4.7
作者：
MCLELLAN, LI;LEWIS, AD;WOLF, CR
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WOLF, CR
影响因子：
3.5
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Banerjee, Atrayee;Trueblood, Max B.;Ercal, Nuran
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Ercal, Nuran
影响因子：
4.8
作者：
Kamencic, H;Griebel, RW;Juurlink, BHJ
通讯作者：
Juurlink, BHJ