A progressive compression model of thoracic spinal cord injury in mice： function assessment and pathological changes in spinal cord

Non-traumatic injury accounts for approximately half of clinical spinal cord injury, including chronic spinal cord compression. However, previous rodent spinal cord compression models are mainly designed for rats, few are available for mice. Our aim is to develop a thoracic progressive compression mice model of spinal cord injury. In this study, adult wild-type C57BL/6 mice were divided into two groups： in the surgery group, a screw was inserted at T9 lamina to compress the spinal cord, and the compression was increased by turning it further into the canal（0.2 mm） post-surgery every 2 weeks up to 8 weeks. In the control group, a hole was drilled into the lamina without inserting a screw. The results showed that Basso Mouse Scale scores were lower and gait worsened. In addition, the degree of hindlimb dysfunction in mice was consistent with the degree of spinal cord compression. The number of motor neurons in the anterior horn of the spinal cord was reduced in all groups of mice, whereas astrocytes and microglia were gradually activated and proliferated. In conclusion, this progressive compression of thoracic spinal cord injury in mice is a preferable model for chronic progressive spinal cord compression injury.

Cellular apoptosis and Caspase-12 expression in a rat model of progressive spinal cord compression

BACKGROUND： Studies have demonstrated that the mechanisms underlying cellular apoptosis signal transduction focus on two pathways： intracellular mitochondria and extracellular death receptor. The current evidence supports that signal transduction of cellular apoptosis also includes endoplasmic reticulum stress signal transduction. OBJECTIVE： To observe Caspase-12 expression and cellular apoptosis following ischemia in rats with progressive spinal cord compression, and to verify the influence of endoplasmic reticulum stress on the apoptosis induced by spinal cord injury. DESIGN, TIME AND SETTING： A randomized, controlled, animal trial was performed at the Institute of Neuroscience in Chongqing Medical University between January and October in 2006. MATERIALS： Immunohistochemical kit, diaminobenzidine, and TUNEL kit were purchased from Beijing Zhongshan Biotechnology, China; rabbit anti-rat Caspase-12 monoclonal antibody was provided by Santa Cruz, USA. METHODS： Sixty Wistar rats, aged 3-4 months, were randomly assigned to a model group （n = 50）, which underwent spinal cord compression in the L1 segment following L1 laminectomy and articular process excision to establish a model of progressive spinal cord compression, and a sham-surgery group （n = 10）, which underwent only laminectomy. Starting with the first day after surgery, the rats were locally anesthetized, the skin was opened, and the screw was rotated by 1/4 of a cycle, twice weekly. MAIN OUTCOME MEASURES： At 3, 7, 14, 21, and 28 days after surgery, rats from each group were anesthetized, and the spinal cords were resected. Pathological changes following spinal cord compression were determined using hematoxylin-eosin staining, Nissl dye, and transmission electron microscopy. The TUNEL method was used to observe neuronal apoptosis in the compressed spinal cord segments. Immunohistochemistry and Western blot were utilized to detect Caspase-12 expression in the compressed segments. RESULTS： Cellular swelling, neural degeneration, and altered endoplasmic reticulum structures were observed at 3 days following compression. Symptoms became gradually aggravated with increasing compression time. Compared with the sham-surgery group, the number of apoptotic neurons was remarkably increased in compressed segments of the model group （P 〈 0.05）, and Caspase-12 expression was also shown to increase （P 〈 0.05）. CONCLUSION： Neuronal apoptosis was a predominant pathological factor resulting in secondary spinal cord injury during progressive spinal cord compression, and Caspase-12 was shown to be possibly involved in neuronal apoptosis induced by progressive spinal cord compression.