Erythropoietin to Treat Spinal Cord Injury: Evaluation of Different Doses and Magnitudes of Trauma in Rats
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Study Design: Experimental spinal cord lesion study.
Objectives: To evaluate the effects of erythropoietin at different doses on neural regeneration in rats undergoing spinal cord injury.
Methods: Anesthetized Wistar rats were submitted to standardized spinal cord injury and randomized into eight groups, receiving different magnitudes of trauma and single or repeated doses of intraperitoneal erythropoietin (500 or 5000 IU/kg of body weight). We evaluated motor function using BBB scores and sensorimotor behavior by observing the rats walking on a horizontal ladder (at 2, 4, and 6 weeks) and performed histological analysis of the spinal cord after euthanasia. We compared the scores between groups using analysis of variance (ANOVA) and Bonferroni multiple comparisons.
Results: The experiments were conducted with 10 animals per group (n = 80), none of which died or were excluded. BBB scores increased over time (meaning recovery) in all groups ( < 0.001 for all). From the fourth week, animals receiving lower trauma and higher erythropoietin doses had higher BBB scores than those receiving lower doses. The total number of steps and correct steps taken on the horizontal ladder increased, and slips decreased over time with treatment in all groups. Although the number of errors was different between moments ( < 0.001), it was not different between groups ( = 0.707). Rats receiving higher impact lesions had more spinal cord necrosis and worse recovery of neuronal fibers than the rest.
Conclusions: Animals receiving a higher dose of erythropoietin and suffering minor trauma showed better and faster neurological recovery. Repeating erythropoietin after a week showed no benefit.