Treatment of experimental spinal cord injury with 3β-methoxy-pregnenolone.

The synthetic derivative of pregnenolone MAP4343 (3β-methoxy-pregnenolone) binds in vitro to microtubule-associated-protein 2 (MAP2), stimulates the polymerization of tubulin, enhances the extension of neurites and protects neurons against neurotoxic agents. Its efficacy was assessed in vivo with the most commonly used thoracic spinal cord compression/contusion models in rats. In the three models used, the post-traumatic subcutaneous injection of MAP4343 significantly improved the recovery of locomotor function after spinal cord injury, as shown by an earlier and more complete recovery compared to vehicle-treated rats. The first injection of MAP4343 could be delayed up to 24h after spinal cord injury with maintained efficiency. The improvement was correlated with the preservation of both dendritic trees of motoneurons in the lumbar spinal cord caudally to the injury site, and of MAP2 at lesion site and in the lumbar spinal cord. The results obtained in three different rat models of spinal cord injury demonstrate the beneficial effects of this therapeutic strategy and identify MAP4343 as a potential treatment for acute spinal cord injury.