Creation of an intramedullary cavity by hemorrhagic necrosis removal 24 h after spinal cord contusion in rats for eventual intralesional implantation of restorative materials

PLoS One. 2017 Apr 17;12(4):e0176105. doi: 10.1371/journal.pone.0176105. eCollection 2017.

Abstract

Intramedullary hemorrhagic necrosis occurs early after spinal cord injury at the site of injury and adjacent segments. It is considered harmful because of its potential to aggravate secondary injury, and to interfere with axonal regeneration; it might also lead to an unfavorable environment for intralesional implants. Removal of hemorrhagic necrosis has been attempted before with variable results. The invasive nature of these procedures carries the risk of exacerbating damage to the injured cord. The overall objective for this study was to test several strategies for non-damaging removal of hemorrhagic necrosis and characterize the resulting cavity looking for a space for future intralesional therapeutic implants in rats with acute cord injury. Rats were subjected to graded cord contusion, and hemorrhagic necrosis was removed after 24h. Three grades of myelotomy (extensive, medium sized, and small) were tested. Using the small surgical approach to debridement, early and late effects of the intervention were determined by histology and by analytical and behavioral analysis. Appearance and capacity of the resulting cavity were characterized. Satisfactory removal of hemorrhagic necrosis was achieved with all three surgical approaches to debridement. However, bleeding in spared cord tissue was excessive after medium sized and extensive myelotomies but similar to control injured rats after small cord surgery. Small surgical approach to debridement produced no swelling nor acute inflammation changes, nor did it affect long-term spontaneous locomotor recovery, but resulted in modest improvement of myelination in rats subjected to both moderate and severe injuries. Cavity created after intervention was filled with 10 to 15 μL of hydrogel. In conclusion, by small surgical approach to debridement, removal of hemorrhagic necrosis was achieved after acute cord contusion thereby creating intramedullary spaces without further damaging the injured spinal cord. Resulting cavities appear suitable for future intralesional placement of pro-reparative cells or other regenerative biomaterials in a clinically relevant model of spinal cord injury.

MeSH terms

  • Animals
  • Contusions / pathology*
  • Contusions / surgery
  • Cordotomy / methods
  • Female
  • Hemorrhage / pathology*
  • Inflammation / pathology
  • Motor Activity / physiology
  • Rats
  • Rats, Long-Evans
  • Recovery of Function / physiology
  • Spinal Cord / pathology*
  • Spinal Cord / surgery
  • Spinal Cord Injuries / pathology*
  • Spinal Cord Injuries / surgery

Grants and funding

This work was supported by the Fund for Health Research (Grant FIS/IMSS/PROT/G13/1217) from the Instituto Mexicano del Seguro Social. GG-S is the author who received the funding. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. URL of funder's website: http://www.imss.gob.mx.