56. Effects of cecompression surgery and erythropoietin combination on a rat model of compressive myelopathy

BACKGROUND CONTEXT

In clinical practice, treatment options for severe myelopathy are currently limited, primarily involving surgical interventions such as decompression surgery. Although decompression surgery is an established treatment in terms of efficacy and safety, the degree of postoperative symptom recovery and the time required for recovery vary among individuals. Therefore, it is worthwhile to explore additional treatment methods that can enhance postoperative outcomes. Erythropoietin (EPO) is a medication known for its hematopoietic effects; however, it has also attracted attention for its neuroprotective and remyelination properties.

PURPOSE

The objective of this study is to investigate the effects of combining EPO administration with decompression surgery in a rat model of cervical compressive myelopathy.

STUDY DESIGN/SETTING

N/A

PATIENT SAMPLE

N/A

OUTCOME MEASURES

N/A

METHODS

Eight-week-old female SD rats were used. After removing the C6 lamina, a hydroexpansive sheet (3 × 5 × 0.7mm) was inserted under the C4/5 lamina to create a chronic spinal cord compression model. Following sheet insertion, weekly behavioral evaluations (Basso, Beattie and Bresnahan score: BBB score, Grid runway test) were conducted, and rats with BBB scores of 13 or lower between weeks 4 and 8 were considered to have developed myelopathy. The BBB score serves as an assessment scale for evaluating the function of a rat's hindlimbs. In the Grid runway test, rats are made to walk on a wire mesh, and the number of times their hindlimbs fall through the grid is measured. To evaluate spinal canal occupancy of sheets, we used micro-CT. Rats with myelopathy were divided into three groups: Control group (sham surgery and subcutaneous saline injection), Decompression group (laminectomy, sheet removal, and subcutaneous saline injection), and Decompression-EPO group (laminectomy, sheet removal, and subcutaneous EPO injection). Behavioral evaluations were conducted for 8 weeks after the onset of myelopathy. Blood samples were collected from the tail vein every 2 weeks, and the administration of EPO was monitored by measuring Hb levels. After 8 weeks, spinal cords were harvested for Luxol fast blue (LFB) staining and immunohistochemical staining (Myeline Basic Protein: MBP, Growth Associated Protein 43: GAP-43, and stuff).

RESULTS

Starting at 4 weeks postintervention, Hb levels in the decompression-EPO group were significantly higher than those in the other two groups. No significant differences were observed in spinal canal occupancy among the three groups at the onset of myelopathy. At 8 weeks postintervention, BBB scores were 12.1(±0.8), 13.4(±1.0), and 14.1(±1.4) for the Control, Decompression, and Decompression-EPO groups, respectively, with a significant difference observed between Decompression-EPO and Control groups (p<0.05). Histologically, significant differences were observed between Decompression-EPO and Control groups in LFB staining, MBP and GAP-43 positive area ratios (p<0.05).

CONCLUSIONS

Focusing on regions with spinal cord compression, LFB staining and MBP-positive area ratios in the corticospinal tract were significantly higher in Decompression-EPO group compared to Control group, suggesting that EPO may have promoted axonal remyelination, contributing to improved behavioral outcomes at 8 weeks postintervention. The efficacy of combined decompression surgery and EPO therapy was confirmed in a rat compressive spinal cord injury model; however, the superiority of this approach over decompression surgery alone could not be established.

FDA Device/Drug Status

Erythropoietin (Not approved for this indication).