Zhou Li-Hua, Wu Wutian
Department of Anatomy, Zhong Shan Medical College, Sun Yat-sen University, Guangzhou, Guangzhou, China.
J Neurotrauma. 2006 Jun;23(6):920-7. doi: 10.1089/neu.2006.23.920.
We conducted a study of whether treatment with glial cell line-derived neurotrophic factor (GDNF) initiated at 2 or 4 weeks after spinal-root avulsion could promote survival and regulate neuronal nitric oxide synthase (nNOS) expression in adult rat spinal motoneurons. By 6 weeks after root avulsion, the treatment given at 2 weeks not only increased motoneuron survival (86.1% vs. 27.9%), but also reversed the atrophy of injured motoneurons and increased their somatic size (101.3% vs. 52.9%) in comparison to the untreated control group of animals. All surviving motoneurons in the GDNF-treated group showed immunoreactivity for choline acetyltransferase. In contrast, GDNF treatment at 4 weeks post-injury failed to promote motoneuron survival (33.1% vs. 27.9%) at 6 weeks compared to the control group. Both the 2- and 4-week post-injury treatments downregulated nNOS expression. This finding suggests that injured adult motoneurons die shortly (a few weeks in the rat) after root avulsion injury, but can be saved from degeneration by treatment within the proper time frame after injury, which in the case of GDNF treatment in rats, appears to be within 2 weeks of the avulsion injury of the spinal root. These findings provide useful information for choosing the best time frame for the potential clinical treatment of brachial plexus avulsion.
我们开展了一项研究，旨在探讨在脊髓神经根撕脱伤后2周或4周开始给予胶质细胞源性神经营养因子（GDNF）进行治疗，是否能够促进成年大鼠脊髓运动神经元的存活并调节神经元型一氧化氮合酶（nNOS）的表达。在神经根撕脱伤后6周时，与未治疗的动物对照组相比，2周时给予治疗不仅提高了运动神经元的存活率（86.1% 对 27.9%），还逆转了受损运动神经元的萎缩并增大了其胞体大小（101.3% 对 52.9%）。GDNF治疗组中所有存活的运动神经元均显示出胆碱乙酰转移酶免疫反应性。相比之下，与对照组相比，损伤后4周给予GDNF治疗在6周时未能促进运动神经元存活（33.1% 对 27.9%）。损伤后2周和4周的治疗均下调了nNOS的表达。这一发现表明，成年大鼠脊髓神经根撕脱伤后，受损的运动神经元在伤后不久（大鼠为几周）就会死亡，但在损伤后的适当时间内进行治疗可使其免于退变，就大鼠GDNF治疗而言，似乎是在脊髓神经根撕脱伤后的2周内。这些发现为选择臂丛神经撕脱伤潜在临床治疗的最佳时间框架提供了有用信息。
