Fagoe Nitish D, Attwell Callan L, Eggers Ruben, Tuinenbreijer Lizz, Kouwenhoven Dorette, Verhaagen Joost, Mason Matthew R J
Laboratory for Neuroregeneration, Netherlands Institute for Neuroscience, an Institute of the Royal Academy of Arts and Sciences, Amsterdam, The Netherlands.
Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, Amsterdam, The Netherlands.
PLoS One. 2016 Mar 2;11(3):e0150141. doi: 10.1371/journal.pone.0150141. eCollection 2016.
The dorsal column lesion model of spinal cord injury targets sensory fibres which originate from the dorsal root ganglia and ascend in the dorsal funiculus. It has the advantages that fibres can be specifically traced from the sciatic nerve, verifiably complete lesions can be performed of the labelled fibres, and it can be used to study sprouting in the central nervous system from the conditioning lesion effect. However, functional deficits from this type of lesion are mild, making assessment of experimental treatment-induced functional recovery difficult. Here, five functional tests were compared for their sensitivity to functional deficits, and hence their suitability to reliably measure recovery of function after dorsal column injury. We assessed the tape removal test, the rope crossing test, CatWalk gait analysis, and the horizontal ladder, and introduce a new test, the inclined rolling ladder. Animals with dorsal column injuries at C4 or T7 level were compared to sham-operated animals for a duration of eight weeks. As well as comparing groups at individual timepoints we also compared the longitudinal data over the whole time course with linear mixed models (LMMs), and for tests where steps are scored as success/error, using generalized LMMs for binomial data. Although, generally, function recovered to sham levels within 2-6 weeks, in most tests we were able to detect significant deficits with whole time-course comparisons. On the horizontal ladder deficits were detected until 5-6 weeks. With the new inclined rolling ladder functional deficits were somewhat more consistent over the testing period and appeared to last for 6-7 weeks. Of the CatWalk parameters base of support was sensitive to cervical and thoracic lesions while hind-paw print-width was affected by cervical lesion only. The inclined rolling ladder test in combination with the horizontal ladder and the CatWalk may prove useful to monitor functional recovery after experimental treatment in this lesion model.
脊髓损伤的背柱损伤模型针对的是起源于背根神经节并在背索中上行的感觉纤维。它具有以下优点:纤维可以从坐骨神经进行特异性追踪,可以对标记纤维进行可验证的完全损伤,并且可以用于研究中枢神经系统中由条件性损伤效应引起的轴突发芽。然而,这种类型损伤导致的功能缺陷较轻,使得评估实验性治疗诱导的功能恢复变得困难。在此,比较了五种功能测试对功能缺陷的敏感性,从而评估它们在可靠测量背柱损伤后功能恢复方面的适用性。我们评估了胶带去除测试、绳索穿越测试、CatWalk步态分析和水平阶梯测试,并引入了一种新测试——倾斜滚动阶梯测试。将C4或T7水平背柱损伤的动物与假手术动物进行为期八周的比较。除了在各个时间点比较组间差异外,我们还使用线性混合模型(LMM)比较了整个时间过程的纵向数据,对于按成功/错误计分步骤的测试,则使用二项数据的广义LMM。虽然一般来说,功能在2 - 6周内恢复到假手术水平,但在大多数测试中,通过整个时间过程的比较我们能够检测到显著的缺陷。在水平阶梯测试中,直到5 - 6周才检测到缺陷。使用新的倾斜滚动阶梯测试时,功能缺陷在测试期内更为一致,并且似乎持续6 - 7周。在CatWalk参数中,支撑基底对颈部和胸部损伤敏感,而后爪印宽度仅受颈部损伤影响。倾斜滚动阶梯测试与水平阶梯测试和CatWalk步态分析相结合,可能有助于监测该损伤模型实验性治疗后的功能恢复。