Interleukin-1 receptor antagonist attenuates the severity of spinal cord ischemic injury in rabbits

Objective Thoracic and thoracoabdominal aortic surgery is sometimes complicated by subacute or delayed paraplegia. Pro-inflammatory cytokine interleukin-1 (IL-1) β has been implicated in extensive inflammation and progressive neurodegeneration after ischemia. Using a rabbit model, we investigated the neuroprotective effects of IL-1 receptor antagonist (IL-1ra) in a temporal fashion. Methods Spinal cord ischemia was induced by aortic cross-clamping in New Zealand White rabbits. The animals were assigned to three groups. Group C (n = 20) received saline (0.2-mL) and Group I (n = 20) received IL-1ra (200-μg/0.2-mL) intrathecally just after reperfusion. Group S (n = 3) underwent sham operation without aortic occlusion. We assessed the neuroprotective effects of IL-1ra by evaluating neurological function, histopathological changes, and in-situ terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL staining). We also measured the levels of Nitric Oxide (NO) and S100β in cerebrospinal fluid (CSF). Each evaluation was performed sequentially within 120 hours after reperfusion. Results Group C showed progressive deterioration of motor function which became statistically significant from 48 hours after the onset of reperfusion ( P < .05, P < .01, P < .001, P < .001 at 48, 72, 96, and 120 hours, respectively). Compared to Group C, a higher number of viable neurons was observed with less severe spinal cord injury in Group I ( P < .01, .05 and .05 at 24, 72, and 120 hours, respectively). TUNEL-positive neurons were also significantly reduced by the administration of IL-1ra ( P