Centre for Neuroscience, Department of Rehabilitation Medicine, 3-88 Corbett Hall, University of Alberta, Edmonton, AB T6E 2G4, Canada.
Exp Neurol. 2013 Sep;247:605-14. doi: 10.1016/j.expneurol.2013.02.013. Epub 2013 Mar 5.
Modeling spinal cord injury (SCI) in animals is challenging because an appropriate combination of lesion location, lesion severity and behavioral testing is essential to analyze recovery of motor function. For particular tests such as single pellet reaching, the contribution of individual descending tracts to recovery has been investigated using specific tract ablation or graded lesions. However, it has not been established whether single pellet reaching is sufficiently sensitive for assessing the efficacy of treatments for cervical SCI (e.g., one of the currently most successful treatment approaches: rehabilitative training). To address this issue, we trained adult rats in single pellet reaching before and after a cervical (C4) spinal lesion. Animals with lesions of increasing severity were grouped into categories based on damage to anatomical structures such as the corticospinal tract (CST) and the rubrospinal tract (RST), two descending motor tracts that have been implicated in fine motor control of the forelimb. We related lesion extent to spontaneous recovery and plasticity-promoting post injury training and found that reaching performance was not correlated with lesion size or the extent of CST or RST injury. Interestingly, the dorsolateral quadrant (DLQ) lesion category, in which the unilateral dorsal CST and most of the unilateral RST are lesioned, was the only category that showed a clear effect of plasticity-promoting treatment (i.e., training), indicating its usefulness as a lesion model for this testing paradigm. The DLQ lesion likely strikes a balance between tissue sparing and functional impairment and is, therefore, best suited to maximize the potential to observe treatment effects of plasticity-promoting treatments using single pellet reaching. Because of the specific lesion size that is necessary to observe treatment effects, the single pellet skilled reaching task can be considered a stringent behavioral test and therefore may be useful for predicting translational success of potential treatments. However, due to the variability in the success rate, the labor-intensive nature, and the limited usefulness to test functional outcome of a wide range of lesion severities, we are hesitant to continue to use single pellet reaching to assess the effectiveness of currently available treatments for cervical SCI.
在动物中模拟脊髓损伤 (SCI) 具有挑战性，因为适当的损伤部位、损伤严重程度和行为测试组合对于分析运动功能的恢复至关重要。对于特定的测试，如单粒颗粒抓取，通过使用特定的束消融或分级损伤来研究个别下降束对恢复的贡献。然而，尚未确定单粒颗粒抓取是否足够敏感，以评估治疗颈椎 SCI 的效果（例如，目前最成功的治疗方法之一：康复训练）。为了解决这个问题，我们在颈椎（C4）脊髓损伤前后对成年大鼠进行了单粒颗粒抓取训练。根据损伤的严重程度将动物分为几类，这些损伤的严重程度基于解剖结构的损伤，例如皮质脊髓束（CST）和红核脊髓束（RST），这两个下降的运动束与前肢的精细运动控制有关。我们将损伤程度与自发恢复和促进损伤后训练的可塑性联系起来，发现抓握表现与损伤大小或 CST 或 RST 损伤程度无关。有趣的是，背外侧象限（DLQ）损伤类别，其中单侧背侧 CST 和大多数单侧 RST 受损，是唯一显示出促进可塑性治疗（即训练）明显效果的类别，表明其作为用于该测试范例的损伤模型的有用性。DLQ 损伤可能在组织保留和功能障碍之间取得平衡，因此最适合最大限度地观察使用单粒颗粒抓取的促进可塑性治疗的治疗效果。由于需要观察治疗效果的特定损伤大小，单粒颗粒熟练抓取任务可以被认为是一项严格的行为测试，因此可能有助于预测潜在治疗方法的转化成功。然而，由于治疗效果的成功率存在差异、劳动强度大以及对广泛损伤严重程度的功能结果测试的实用性有限，我们不愿意继续使用单粒颗粒抓取来评估目前用于治疗颈椎 SCI 的治疗方法的有效性。
