Interdepartmental Program for Neuroscience, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Exp Neurol. 2012 Feb;233(2):758-66. doi: 10.1016/j.expneurol.2011.11.034. Epub 2011 Dec 8.
Previous studies involving injuries to the nerves of the cauda equina and the conus medullaris have shown that lumbosacral ventral root avulsion in rat models results in denervation and dysfunction of the lower urinary tract, retrograde and progressive cell death of the axotomized motor and parasympathetic neurons, as well as the emergence of neuropathic pain. Root reimplantation has also been shown to ameliorate several of these responses, but experiments thus far have been limited to studying the effects of lesion and reimplantation local to the lumbosacral region. Here, we have expanded the region of investigation after lumbosacral ventral root avulsion and reimplantation to include the thoracolumbar sympathetic region of the spinal cord. Using a retrograde tracer injected into the major pelvic ganglion, we were able to define the levels of the spinal cord that contain sympathetic preganglionic neurons innervating the lower urinary tract. We have conducted studies on the effects of the lumbosacral ventral root avulsion and reimplantation models on the afferent innervation of the dorsal horn and autonomic nuclei at both thoracolumbar and lumbosacral levels through immunohistochemistry for the markers calcitonin gene-related peptide (CGRP) and vesicular glutamate transporter 1 (VGLUT1). Surprisingly, our experiments reveal a selective and significant decrease of CGRP-positive innervation in the dorsal horn at thoracolumbar levels that is partially restored with root reimplantation. However, no similar changes were detected at the lumbosacral levels despite the injury and repair targeting efferent neurons, and being performed at the lumbosacral levels. Despite the changes evident in the thoracolumbar dorsal horn, we find no changes in afferent innervation of the autonomic nuclei at either sympathetic or parasympathetic segmental levels by CGRP or VGLUT1. We conclude that even remote, efferent root injuries and repair procedures can have an effect on remote and non-lesioned sensory systems sharing common peripheral ganglia.
先前涉及马尾和脊髓圆锥神经损伤的研究表明，在大鼠模型中，腰骶部腹根撕脱导致下尿路去神经和功能障碍，轴突切断的运动和副交感神经元逆行和进行性细胞死亡，以及出现神经病理性疼痛。根再植入也已被证明可以改善其中的一些反应，但到目前为止，实验仅限于研究腰骶部区域内的损伤和再植入的影响。在这里，我们在腰骶部腹根撕脱和再植入后扩大了研究区域，包括脊髓的胸腰交感区域。通过向主要盆神经节注射逆行示踪剂，我们能够确定包含支配下尿路的交感节前神经元的脊髓水平。我们通过免疫组织化学检测降钙素基因相关肽 (CGRP) 和囊泡谷氨酸转运体 1 (VGLUT1) 标志物，对腰骶部腹根撕脱和再植入模型对背角和自主核传入神经支配的影响进行了研究。令人惊讶的是，我们的实验揭示了背角在胸腰段水平上 CGRP 阳性神经支配的选择性和显著减少，而根再植入部分恢复了这种减少。然而，尽管针对传出神经元进行了损伤和修复，并在腰骶部进行了损伤和修复，但在腰骶部水平上没有检测到类似的变化。尽管在胸腰段背角明显发生了变化，但我们发现 CGRP 或 VGLUT1 对自主神经核的传入神经支配在交感或副交感节段水平上均无变化。我们得出结论，即使是远处的传出神经根损伤和修复程序也会对共享共同外周神经节的远程和未受损的感觉系统产生影响。
