Neurotrophin-3 modified hyaluronan-methylcellulose hydrogel promotes neurological function in rats with spinal cord injury / 中国组织工程研究

ABSTRACT

BACKGROUND: Hyaluronan-methylcellulose hydrogel cannot only be conjugated with short peptide sequences and growth factors to achieve sustained release, but also has a role in blocking dural defects and reducing inflammation. It is an ideal biomaterial for the treatment of spinal cord injury. OBJECTIVE: To investigate the effect of neurotrophin-3 modified hyaluronan-methylcellulose (HAMC-NT-3) hydrogel on the recovery of neurological function in rats with spinal cord injury. METHODS: Fifty-four female Sprague-Dawley rats (provided by the Experimental Animal Center of the Academy of Military Medical Sciences in China) were randomly divided into three groups (n=18 per group) . The sham group only underwent T10 laminectomy. In the model group and the experimental group, an aneurysm clip was used to establish spinal cord injury models after T10 laminectomy. The experimental group was locally injected with HAMC-NT-3 hydrogel. The Basso Beattie Bresnahan function scoring was performed at 1 day, 1, 2, 3, 4, 5, 6, 7, and 8 weeks after surgery. The inclined plane test was performed at 4, 6 and 8 weeks after surgery to evaluate the recovery of hindlimb motor function. ELISA was used to detect the concentrations of inflammatory factors in the spinal cord at 1 week after surgery. Immunohistochemical staining was used to observe the area of syringomyelia, glial fibrillary acidic protein expression and nerve regeneration at 8 weeks after surgery. RESULTS AND CONCLUSION: (1) The Basso Beattie Bresnahan scores of the model group and the experimental group were lower than those of the sham group at various time points after surgery (P < 0.05) . The Basso Beattie Bresnahan scores of the experimental group were higher than those of the model group at 4-8 weeks after surgery (P < 0.05) . (2) In the inclined plane test, the maximum inclined angles of the model group and the experimental group at each time point after surgery were lower than that of the sham group (P < 0.05) . The maximum inclined angles of the experimental group at 6 and 8 weeks after surgery were higher than those of the sham group (P < 0.05) . (3) The concentrations of tumor necrosis factor-α, interleukin-1β, interleukin-6 and interleukin-10 in the experimental group and the model group were higher than those in the sham group (P < 0.05) . The concentrations of tumor necrosis factor-α, interleukin-1β and interleukin-6 in the experimental group were lower than those in the model group (P < 0.05) . The concentration of interleukin-10 in the experimental group was higher than that in the model group (P < 0.05) . (4) Immunohistochemical staining showed that the expression levels of glial fibrillary acidic protein in the experimental group and the model group were higher than those in the sham group, while the expression of glial fibrillary acidic protein in the experimental group was lower than that in the model group. The area of syringomyelia in the experimental group was smaller than that in the model group (P < 0.05) . These results indicate that local injection of HAMC-NT-3 hydrogel can effectively inhibit inflammation as well as astrocyte activation and proliferation, reduce fibrous scar formation, and promote the protection of nerve tissue and the recovery of hindlimb motor function after spinal cord injury.