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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.