Xu W, Chi L, Xu R, Ke Y, Luo C, Cai J, Qiu M, Gozal D, Liu R
Department of Pediatrics, Kosair Children's Hospital Research Institute, University of Louisville, Louisville, KY 40202, USA.
Spinal Cord. 2005 Apr;43(4):204-13. doi: 10.1038/sj.sc.3101674.
Experimental laboratory investigation of the role and pathways of reactive oxygen species (ROS)-mediated motor neuron cell death in a mouse model of compression spinal cord injury.
To analyze ROS-mediated oxidative stress propagation and signal transduction leading to motor neuron apoptosis induced by compression spinal cord injury.
University of Louisville Health Science Center.
Adult C57BL/6J mice and transgenic mice overexpressing SOD1 were severely lesioned at the lumbar region by compression spinal cord injury approach. Fluorescent oxidation, oxidative response gene expression and oxidative stress damage markers were used to assay spinal cord injury-mediated ROS generation and oxidative stress propagation. Biochemical and immunohistochemical analyses were applied to define the ROS-mediated motor neuron apoptosis resulted from compression spinal cord injury.
ROS production was shown to be elevated in the lesioned spinal cord as detected by fluorescent oxidation assays. The early oxidative stress response markers, NF-kappaB transcriptional activation and c-Fos gene expression, were significantly increased after spinal cord injury. Lipid peroxidation and nucleic acid oxidation were also elevated in the lesioned spinal cord and motor neurons. Cytochrome c release, caspase-3 activation and apoptotic cell death were increased in the spinal cord motor neuron cells after spinal cord injury. On the other hand, transgenic mice overexpressing SOD1 showed lower levels of steady-state ROS production and reduction of motor neuron apoptosis compared to that of control mice after spinal cord injury.
These data together provide direct evidence to demonstrate that the increased production of ROS is an early and likely causal event that contributes to the spinal cord motor neuron death following spinal cord injury. Thus, antioxidants/antioxidant enzyme intervention combined with other therapy may provide an effective approach to alleviate spinal cord injury-induced motor neuron damage and motor dysfunction.
在压缩性脊髓损伤小鼠模型中对活性氧（ROS）介导的运动神经元细胞死亡的作用和途径进行实验性实验室研究。
分析ROS介导的氧化应激传播和信号转导，其导致压缩性脊髓损伤诱导的运动神经元凋亡。
路易斯维尔大学健康科学中心。
通过压缩性脊髓损伤方法对成年C57BL/6J小鼠和过表达SOD1的转基因小鼠进行严重的腰部损伤。使用荧光氧化、氧化反应基因表达和氧化应激损伤标志物来检测脊髓损伤介导的ROS生成和氧化应激传播。应用生化和免疫组织化学分析来确定由压缩性脊髓损伤导致的ROS介导的运动神经元凋亡。
通过荧光氧化测定法检测到，损伤脊髓中的ROS产生增加。脊髓损伤后，早期氧化应激反应标志物NF-κB转录激活和c-Fos基因表达显著增加。损伤脊髓和运动神经元中的脂质过氧化和核酸氧化也升高。脊髓损伤后，脊髓运动神经元细胞中的细胞色素c释放、caspase-3激活和凋亡细胞死亡增加。另一方面，与脊髓损伤后的对照小鼠相比，过表达SOD1的转基因小鼠显示出较低水平的稳态ROS产生和运动神经元凋亡减少。
这些数据共同提供了直接证据，证明ROS产生增加是脊髓损伤后导致脊髓运动神经元死亡的早期且可能的因果事件。因此，抗氧化剂/抗氧化酶干预与其他疗法相结合可能提供一种有效的方法来减轻脊髓损伤诱导的运动神经元损伤和运动功能障碍。
