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预防性利鲁唑减轻脊髓牵张中的氧化应激损伤。

Prophylactic Riluzole Attenuates Oxidative Stress Damage in Spinal Cord Distraction.

机构信息

1 Bioengineering Department, University of Texas at Dallas , Richardson, Texas.

2 Surgery Department, University of Texas Southwestern Medical Center , Dallas, Texas.

出版信息

J Neurotrauma. 2018 Jun 15;35(12):1319-1328. doi: 10.1089/neu.2017.5494. Epub 2018 Mar 20.

Abstract

Spinal cord injury (SCI) without radiographical abnormalities (SCIWORA) presents a significant challenge because of the loss of function despite an apparent normal anatomy. The cause of dysfunction is not understood, and specific treatment options are lacking. Some scoliosis corrective surgeries result in SCIWORA, where stretching of the spinal cord can lead to vascular compromise and hypoxia. The iatrogenic nature of this injury allows for the implantation of neuroprotective strategies that are designed to prevent damage. We utilized a model of atraumatic SCI to evaluate the efficacy of the sodium-channel blocker, riluzole, as a prophylactic neuroprotectant. As expected, the stretch injury caused a significant reduction in intraparenchymal oxygen in distraction (-53.09 ± 22.23%) and riluzole pre-treated distraction animals (-43.04 ± 22.86%). However, in contrast to the oxidative stress and metabolic impairments observed in vehicle-treated distraction animals, in which protein carbonylation increased significantly (5.88 ± 1.3 nmol/mL), riluzole kept these levels within the normal range (1.8 ± 1.0 nmol/mL). This neurprotection also prevented ventral motor neuron hypoplasia and pyknosis, characteristic features of this atraumatic SCI model, and maintained normal gait function (e.g., stride length and stance time). This study provides evidence for the use of prophylactic neuroprotective strategies in which thoracic or spine surgeries present the risk of causing atraumatic SCI.

摘要

脊髓损伤(SCI)无影像学异常(SCIWORA)是一个重大挑战,因为尽管解剖结构正常,但功能丧失。功能障碍的原因尚不清楚,也缺乏特定的治疗方法。一些脊柱侧凸矫形手术会导致 SCIWORA,其中脊髓的拉伸会导致血管损伤和缺氧。这种医源性损伤允许植入神经保护策略,旨在预防损伤。我们使用了一种无创伤性 SCI 模型来评估钠通道阻滞剂利鲁唑作为预防神经保护剂的疗效。正如预期的那样,拉伸损伤导致牵张时脑实质内氧分压显著降低(-53.09±22.23%)和利鲁唑预处理牵张动物(-43.04±22.86%)。然而,与在载体处理的牵张动物中观察到的氧化应激和代谢损伤不同,在其中蛋白质羰基化显著增加(5.88±1.3 nmol/mL),利鲁唑将这些水平保持在正常范围内(1.8±1.0 nmol/mL)。这种神经保护还防止了腹侧运动神经元的萎缩和固缩,这是这种无创伤性 SCI 模型的特征,并维持了正常的步态功能(例如,步幅和站立时间)。这项研究为预防性神经保护策略的使用提供了证据,这些策略可用于存在导致无创伤性 SCI 风险的胸或脊柱手术。

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