Establishment and evaluation of a rat model of complete transected spinal cord injury*☆

BACKGROUND： The establishment of a rat model of complete transected spinal cord injury lacks technological specifications. The current models lack concordance and reliability, and the death rate of the experimental animals is high. Therefore, there is a great need for a reliable model to apply clinical applications of therapy. OBJECTIVE： To construct a rat model of complete transected spinal cord injury characterized by stability, reproducibility, and a high animal survival rate. DESIGN： Completely randomized controlled study. SETTING： Department of Neurosurgery, Xiangya Hospital of Central South University. MATERIALS： Fifty-five healthy specific pathogen free grade adult female Sprague Dawley rats were provided by the Experimental Animal Department, Xiangya Medical College, Central South University. Olympus BX51 imaging collecting analytic system was provided by Olympus Company, Japan; and SEN-7203 Nihon-Kohden electrical stimulator by Nihon Kohden, Japan. METHODS： This study was performed at the Laboratory of Neurosurgery, Xiangya Hospital of Central South University from April to June 2006. Experimental grouping： 55 rats were randomly divided into model group （n = 40） and sham surgery group （n = 15）. In the model group, a self-made sliver hook was passed through the ventral side to support the spinal cord at the T12 segment and to shear it off. A complete transected spinal cord, 2 mm in length, was resected. In the sham surgery group, the spinal cord was identically exposed. The dura mater of the spinal cord was cut open, but the spinal cord was not damaged. MAIN OUTCOME MEASURES： Histopathological changes after spinal cord injury at L2 segment were observed subsequent to hematoxylin and eosin staining under optical microscopy. Olympus BX51 imaging collecting analytic system was used to count spinal cord ventral horn neurons. Motor function of rat hindlimb was evaluated with the Basso, Beattie and Bresnahan （BBB） scale. Paraplegia was evaluated as 0 point, and complete normality as

Establishment and evaluation of a rat model of complete transected spinal cord injury

BACKGROUND: The establishment of a rat model of complete transected spinal cord injury lacks technological specifications. The current models lack concordance and reliability, and the death rate of the experimental animals is high. Therefore, there is a great need for a reliable model to apply clinical applications of therapy.OBJECTIVE: To construct a rat model of complete transected spinal cord injury characterized by stability, reproducibility, and a high animal survival rate. DESIGN: Completely randomized controlled study.SETTING: Department of Neurosurgery, Xiangya Hospital of Central South University.MATERIALS: Fifty-five healthy specific pathogen free grade adult female Sprague Dawley rats were provided by the Experimental Animal Department, Xiangya Medical College, Central South University. Olympus BX51 imaging collecting analytic system was provided by Olympus Company, Japan; and SEN-7203 Nihon-Kohden electrical stimulator by Nihon Kohden, Japan. METHODS: This study was performed at the Laboratory of Neurosurgery, Xiangya Hospital of Central South University from April to June 2006. Experimental grouping: 55 rats were randomly divided into model group (n = 40) and sham surgery group (n = 15). In the model group, a self-made sliver hook was passed through the ventral side to support the spinal cord at the T12 segment and to shear it off. A complete transected spinal cord, 2 mm in length, was resected. In the sham surgery group, the spinal cord was identically exposed. The dura mater of the spinal cord was cut open, but the spinal cord was not damaged. MAIN OUTCOME MEASURES: Histopathological changes after spinal cord injury at L2 segment were observed subsequent to hematoxylin and eosin staining under optical microscopy. Olympus BX51 imaging collecting analytic system was used to count spinal cord ventral horn neurons. Motor function of rat hindlimb was evaluated with the Basso, Beattie and Bresnahan (BBB) scale. Paraplegia was evaluated as 0 point, and complete normality as 21 points. Somatosensory-evoked potential was measured using Nihon-Kohden electric stimulator at 21 days post-operation. RESULTS: A total of 82% (33/40) rats survived longer than 30 days after modeling. Pathological changes of spinal cord tissue: degenerative and necrotic pathological changes appeared in the model group after surgery; for example, neuronal swelling, chromatinolysis, and karyopyknosis. The spinal cord in the sham surgery group displayed mild edema 24 hours after surgery, gradually recovering to normal levels. Quantification of spinal cord ventral horn neurons: the number of spinal cord ventral horn neurons in the model group was less than in the sham surgery group at 24 hours, as well as 7 and 21 days after surgery (P<0.01); while, the number at 7 and 21 days after surgery decreased compared to 24 hours after surgery (P < 0.01). Motor function changes: Rats in the sham operation group moved lightly abnormally following anesthesia recovery and then moved normally 7 days after surgery. BBB scores in the model group were less than in the sham surgery group 21 days after surgery (P < 0.01). BBB scores of both lower extremities increased slightly 7 days after surgery (P<0.01); however, voluntary motor function of both lower extremities was still not recovered 30 days after surgery. Changes of somatosensory-evoked potential: wave form of somatosensory-evoked potential was normal in the sham surgery group 21 days after surgery, but recovered wave form was not recorded in the model group. CONCLUSION: Results from spinal cord histopathology, cytology, motor function, and somatosensory-evoked potential suggested that the complete transected spinal cord injury model in this study was stable, reliable, and reproducible. Furthermore, the survival rate of experimental animals was high.