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.