Ye Junli, Cao Li, Cui Ruiyao, Huang Aijun, Yan Zhiyong, Lu Changlin, He Cheng
Department of Neurobiology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China.
Brain Res. 2004 Jan 30;997(1):30-9. doi: 10.1016/j.brainres.2003.10.036.
Ciliary neurotrophic factor (CNTF) has been implicated in the pathophysiology of injury to the central nervous system. The rapid increase in CNTF production following spinal cord injury (SCI) in rats is thought to serve a role in the neuronal survival and functional recovery. In this study, 40 SD rats were divided into four groups: sham-operated group, saline-treated group, 5- and 10-microg CNTF group. Saline and CNTF were given through lumbar intrathecal catheter for 10 days after T10 segment of spinal cord were injured by modified Allen contusion method. Animals were behaviorally tested for 6 weeks using the Basso, Beattie, Bresnahan locomotor rating scale and inclined plane test. At the end of 6 week, rubrospinal neurons of five rats in each group were labeled by retrograde transport of the horseradish peroxidase (HRP) from the lesion site, and then the labeled red nucleus neuron (RN) numbers were counted. Additional rats were histologically assessed for tissue sparing and neuronal loss and reactive gliosis at the injury site and adjacent areas. Rats treated with CNTF regained greater improvements in hindlimb function than controls. The amount of spared tissue was significantly higher in CNTF-treated animals than in controls. After CNTF treatment, the number of HRP-labeled RN neurons were significantly increased. Astrocytes and microglia reactivity was more pronounced in CNTF-treated animals than in controls. These results indicate that intrathecal infusion of exogenous CNTF following SCI may significantly reduce tissue damage and protect the rubrospinal descending tracks and enhances functional recovery, and may also induce more gliosis.
睫状神经营养因子（CNTF）与中枢神经系统损伤的病理生理学有关。大鼠脊髓损伤（SCI）后CNTF产量的快速增加被认为在神经元存活和功能恢复中起作用。在本研究中，40只SD大鼠分为四组：假手术组、生理盐水治疗组、5微克和10微克CNTF组。采用改良的Allen挫伤法损伤脊髓T10节段后，通过腰段鞘内导管给予生理盐水和CNTF，持续10天。使用Basso、Beattie、Bresnahan运动评分量表和斜面试验对动物进行6周的行为测试。在6周结束时，通过辣根过氧化物酶（HRP）从损伤部位逆行转运对每组5只大鼠的红核脊髓神经元进行标记，然后计算标记的红核神经元（RN）数量。对另外的大鼠进行组织学评估，以观察损伤部位及相邻区域的组织保留情况、神经元丢失和反应性胶质增生。接受CNTF治疗的大鼠后肢功能恢复比对照组更好。CNTF治疗组动物的保留组织量明显高于对照组。CNTF治疗后，HRP标记的RN神经元数量显著增加。与对照组相比，接受CNTF治疗的动物中星形胶质细胞和小胶质细胞的反应更明显。这些结果表明，SCI后鞘内注入外源性CNTF可显著减少组织损伤，保护红核脊髓下行通路，促进功能恢复，还可能诱导更多的胶质增生。
