Sodium channel blockade with phenytoin protects spinal cord axons, enhances axonal conduction, and improves functional motor recovery after contusion SCI
Sodium channel blockade with phenytoin protects spinal cord axons, enhances axonal conduction, and improves functional motor recovery after contusion SCI
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DOI：
10.1016/j.expneurol.2004.04.001
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发表时间：
2004-08-01
影响因子：
5.3
通讯作者：
Waxman, SG
中科院分区：
文献类型：
--
作者：
Hains, BC;Saab, CY;Waxman, SG
通过电压门控钠通道（VGSC）的细胞内钠积累是导致创伤性脊髓损伤（SCI）后脊髓轴突解剖学变性和不良功能结果的级联反应中的重要事件。在这项研究中，我们假设苯妥英钠，钠通道阻滞剂，将导致脊髓损伤后的轴突保护与功能恢复的改善。成年雄性Sprague-Dawley大鼠在喂食正常食物或含苯妥英的食物后发生T9挫伤SCI;损伤时苯妥英的血清水平在治疗范围内。在损伤后的不同时间点，对损伤体积、轴突变性、轴突传导和功能性运动恢复进行定量评估。与对照组相比，苯妥英治疗的动物表现出病变中心周围灰质和白色物质破坏程度的降低，保留了病变部位头侧的背侧皮质脊髓束（dCST）和背柱（DC）系统内以及病变部位尾侧的背外侧索（DLF）内的轴突，并增强了整个病变部位的轴突传导。在苯妥英治疗的动物中观察到熟练运动功能测量的性能改善。基于这些结果，我们得出结论，苯妥英钠提供神经保护和改善功能的结果后，实验性SCI，它值得进一步检查作为一个潜在的治疗策略在人类SCI。(C)2004年爱思唯尔公司All rights reserved.
Accumulation of intracellular sodium through voltage-gated sodium channels (VGSCs) is an important event in the cascade leading to anatomic degeneration of spinal cord axons and poor functional outcome following traumatic spinal cord injury (SCI). In this study, we hypothesized that phenytoin, a sodium channel blocker, would result in protection of axons with concomitant improvement of functional recovery after SCI. Adult male Sprague-Dawley rats underwent T9 contusion SCI after being fed normal chow or chow containing phenytoin; serum levels of phenytoin were within therapeutic range at the time of injury. At various timepoints after injury, quantitative assessment of lesion volumes, axonal degeneration, axonal conduction, and functional locomotor recovery were performed. When compared to controls, phenytoin-treated animals demonstrated reductions in the degree of destruction of gray and white matter surrounding the lesion epicenter, sparing of axons within the dorsal corticospinal tract (dCST) and dorsal column (DC) system rostral to the lesion site, and within the dorsolateral funiculus (DLF) caudal to the lesion site, and enhanced axonal conduction across the lesion site. Improved performance in measures of skilled locomotor function was observed in pbenytoin-treated animals. Based on these results, we conclude that phenytoin provides neuroprotection and improves functional outcome after experimental SCI, and that it merits further examination as a potential treatment strategy in human SCI. (C) 2004 Elsevier Inc. All rights reserved.