A decrease in the neuroprotective effects of acute spinal cord decompression according to injury severity: introducing the concept of a ceiling effect

Abstract

OBJECTIVE Acute traumatic spinal cord injury (tSCI) is followed by a prolonged period of secondary neuroglial cell death. Neuroprotective interventions, such as surgical spinal cord decompression, aim to mitigate secondary injury. In this study, the authors explore whether the effect size of posttraumatic neuroprotective spinal cord decompression varies with injury severity. METHODS Seventy-one adult female Long Evans rats were subjected to a thoracic tSCI using a third-generation spinal contusion device. Moderate and severe tSCI were defined by recorded impact force delivered to the spinal cord. Immediately after injury (< 15 minutes), treatment cohorts underwent either a decompressive durotomy or myelotomy. Functional recovery was documented using the Basso, Beattie, and Bresnahan locomotor scale, and tissue sparing was documented using histological analysis. RESULTS Moderate and severe injuries were separated at a cutoff point of 231.8 kdyn peak impact force based on locomotor recovery at 8 weeks after injury. Durotomy improved hindlimb locomotor recovery 8 weeks after moderate trauma (p < 0.01), but not after severe trauma (p > 0.05). Myelotomy led to increased tissue sparing (p < 0.0001) and a significantly higher number of spared motor neurons (p < 0.05) in moderate trauma, but no such effect was noted in severely injured rats (p > 0.05). Within the moderate injury group, myelotomy also resulted in significantly more spared tissue when compared with durotomy-only animals (p < 0.01). CONCLUSIONS These results suggest that the neuroprotective effects of surgical spinal cord decompression decrease with increasing injury severity in a rodent tSCI model.