Wen Junxiang, Sun Dongming, Tan Jun, Young Wise
1 Department of Cell Biology and Neuroscience, Rutgers, the State University of New Jersey , Piscataway, New Jersey.
2 Department of Orthopaedics, Tongji University School of Medicine , Shanghai, China .
J Neurotrauma. 2015 Jun 15;32(12):875-92. doi: 10.1089/neu.2013.3321. Epub 2015 Mar 12.
The purpose of this study is to develop a rat lumbosacral spinal cord injury (SCI) model that causes consistent motoneuronal loss and behavior deficits. Most SCI models focus on the thoracic or cervical spinal cord. Lumbosacral SCI accounts for about one third of human SCI but no standardized lumbosacral model is available for evaluating therapies. Twenty-six adult female Sprague-Dawley rats were randomized to three groups: sham (n=9), 25 mm (n=8), and 50 mm (n=9). Sham rats had laminectomy only, while 25 mm and 50 mm rats were injured by dropping a 10 g rod from a height of 25 mm or 50 mm, respectively, onto the L4-5 spinal cord at the T13/L1 vertebral junction. We measured footprint length (FL), toe spreading (TS), intermediate toe spreading (ITS), and sciatic function index (SFI) from walking footprints, and static toe spreading (STS), static intermediate toe spreading (SITS), and static sciatic index (SSI) from standing footprints. At six weeks, we assessed neuronal and white matter loss, quantified axons, diameter, and myelin thickness in the peroneal and tibial nerves, and measured cross-sectional areas of tibialis anterior and gastrocnemius muscle fibers. The result shows that peroneal and tibial motoneurons were respectively distributed in 4.71 mm and 5.01 mm columns in the spinal cord. Dropping a 10-g weight from 25 mm or 50 mm caused 1.5 mm or 3.75 mm gaps in peroneal and tibial motoneuronal columns, respectively, and increased spinal cord white matter loss. Fifty millimeter contusions significantly increased FL and reduced TS, ITS, STS, SITS, SFI, and SSI more than 25 mm contusions, and resulted in smaller axon and myelinated axon diameters in tibial and peroneal nerves and greater atrophy of gastrocnemius and anterior tibialis muscles, than 25 mm contusions. This model of lumbosacral SCI produces consistent and graded loss of white matter, motoneuronal loss, peripheral nerve axonal changes, and anterior tibialis and gastrocnemius muscles atrophy in rats.
本研究的目的是建立一种大鼠腰骶部脊髓损伤（SCI）模型，该模型可导致一致的运动神经元损失和行为缺陷。大多数SCI模型关注的是胸段或颈段脊髓。腰骶部SCI约占人类SCI的三分之一，但尚无标准化的腰骶部模型可用于评估治疗方法。将26只成年雌性Sprague-Dawley大鼠随机分为三组：假手术组（n = 9）、25毫米组（n = 8）和50毫米组（n = 9）。假手术组大鼠仅进行椎板切除术，而25毫米组和50毫米组大鼠分别从25毫米或50毫米的高度将一根10克的棒 dropped 到T13/L1椎体交界处的L4-5脊髓上。我们从行走足迹中测量足迹长度（FL）、趾展度（TS）、中间趾展度（ITS）和坐骨神经功能指数（SFI），并从站立足迹中测量静态趾展度（STS）、静态中间趾展度（SITS）和静态坐骨神经指数（SSI）。在六周时，我们评估神经元和白质损失，量化腓总神经和胫神经中的轴突、直径和髓鞘厚度，并测量胫骨前肌和腓肠肌肌纤维的横截面积。结果表明，腓总运动神经元和胫运动神经元分别分布在脊髓中4.71毫米和5.01毫米的柱内。从25毫米或50毫米高度 dropping 一个10克的重物分别导致腓总运动神经元柱和胫运动神经元柱出现1.5毫米或3.75毫米的间隙，并增加脊髓白质损失。与25毫米挫伤相比，50毫米挫伤显著增加了FL，并使TS、ITS、STS、SITS、SFI和SSI降低得更多，导致胫神经和腓总神经中的轴突和有髓轴突直径更小，腓肠肌和胫骨前肌萎缩更严重。这种腰骶部SCI模型在大鼠中产生了一致且分级的白质损失、运动神经元损失、周围神经轴突变化以及胫骨前肌和腓肠肌萎缩。
