摘要
Inflammation is a major cause of neuronal injury after spinal cord injury. We hypothesized that inhibiting caspase-1 activation may reduce neuroinflammation after spinal cord injury, thus producing a protective effect in the injured spinal cord. A mouse model of T9 contusive spinal cord injury was established using an Infinite Horizon Impactor, and VX-765, a selective inhibitor of caspase-1, was administered for 7 successive days after spinal cord injury. The results showed that:(1) VX-765 inhibited spinal cord injury-induced caspase-1 activation and interleukin-1β and interleukin-18 secretion.(2) After spinal cord injury, an increase in M1 cells mainly came from local microglia rather than infiltrating macrophages.(3) Pro-inflammatory Th1 Th17 cells were predominant in the Th subsets. VX-765 suppressed total macrophage infiltration, M1 macrophages/microglia, Th1 and Th1 Th17 subset differentiation, and cytotoxic T cells activation;increased M2 microglia;and promoted Th2 and Treg differentiation.(4) VX-765 reduced the fibrotic area, promoted white matter myelination, alleviated motor neuron injury, and improved functional recovery. These findings suggest that VX-765 can reduce neuroinflammation and improve nerve function recovery after spinal cord injury by inhibiting caspase-1/interleukin-1β/interleukin-18. This may be a potential strategy for treating spinal cord injury. This study was approved by the Animal Care Ethics Committee of Bengbu Medical College(approval No. 2017-037) on February 23, 2017.
基金
supported by the National Natural Science Foundation of China,Nos.81772321,82072416(both to HZL)。
作者简介
Correspondence to:He-Zuo Lü,MD,PhD,lhz233003@163.com,https://orcid.org/0000-0002-3889-835X;Correspondence to:Jian-Guo Hu,MD,PhD,jghu9200@163.com,https://orcid.org/0000-0002-9055-874X;Jing Chen,contributed equally to this work;Yu-Qing Chencontributed equally to this work。
