VX-765 reduces neuroinflammation after spinal cord injury in mice

Autor: Jing Chen, Yu-Qing Chen, Yu-Jiao Shi, Shu-Qin Ding, Lin Shen, Rui Wang, Qi-Yi Wang, Cheng Zha, Hai Ding, Jian-Guo Hu, He-Zuo Lü
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Neural Regeneration Research, Vol 16, Iss 9, Pp 1836-1847 (2021)
Druh dokumentu: article
ISSN: 1673-5374
DOI: 10.4103/1673-5374.306096
Popis: 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 Th1Th17 cells were predominant in the Th subsets. VX-765 suppressed total macrophage infiltration, M1 macrophages/microglia, Th1 and Th1Th17 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.
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