ANTI-INFLAMMATORY AND NEUROPROTECTIVE EFFECTS OF INFLAMMASOME INHIBITORS FOLLOWING CONTUSION SPINAL CORD INJURY

Following contusion spinal cord injury, severe neuroinflammation develops in the affected area. Activated inflammasomes play a key role in initiating the pro-inflammatory cascade. The aim of this study was to investigate the extent of morphological and functional regeneration achievable after spinal cord injury through inhibition of the NLRP3 inflammasome alone or combined inhibition of NLRP3 and NLRC4 inflammasomes. In our experiments contusion spinal cord injury was induced at the T10 level in Sprague–Dawley rats. Animals were treated for four days with either a selective NLRP3 inhibitor (MCC950) or a dual NLRP3/NLRC4 inhibitor (C75) via intraperitoneal injection. Control groups received no treatment or vehicle only. In short-term experiments, inflammatory gene expression was analyzed by qPCR, and microglia/macrophage responses were assessed using immunohistochemistry. In long-term survival groups, intact or regenerated spinal tracts were identified by retrograde labeling, and locomotor function was evaluated using video-based gait analysis. Both MCC950 and C75 treatments significantly reduced pro-inflammatory gene expression in the injured spinal cord. Microglia/macrophage density was markedly decreased in treated animals at three and seven days post-injury. The number of retrogradely labeled neurons was significantly higher in both treatment groups. Morphological analyses demonstrated substantial neuroprotection, while functional assessments revealed significant improvements in motor performance. In conclusion, inhibition of the NLRP3 inflammasome alone or in combination with NLRC4 effectively attenuates neuroinflammation following contusion spinal cord injury, leading to long-term preservation of spinal pathways and overall neuroprotection.