INTRA-SPINAL ADMINISTRATION OF NETRIN-1 PROMOTES RECOVERY OF VOLUNTARY LOCOMOTION AFTER COMPLETE SPINAL CORD INJURY IN A RAT MODEL.

HR QUINTÁ

Congreso; Sociedad Argentina de Investigación Clinica SAIC; 2018

SAIC

For decades, axon regeneration has been considered the Holy Grail for spinal cord injury (SCI) repair. The ?key? has been thought to be the regeneration of the long motor and sensory tracts that are interrupted by SCI. Worldwide scientists focus their research in promoting re-growth of these axonal tracts to achieve recovery of paralysis, restoration of autonomic function and re-gain of sensation. According to this background, we focus the treatment of this traumatic pathology by using an axonal chemoattractant protein, which is involved in axonal growth during the embryonic development. This protein, Netrin-1, was described 20 years ago, as an axonal repulsive molecule expressed in embryonic tissues in the form of gradients. However, it has been described that it also participates in axonal guidance by promoting axonal growth as opposed to what was believed.Using a transection SCI rat model, it was observed a significant recovery of locomotion in rats treated with Netrin-1 intra-spinally. Locomotion scores 21 days after injury showed a significant improvement of locomotor function in rats treated acutely with Netrin-1 as compared to control animals treated with vehicle, which showed a complete absence of locomotor recovery. This result correlated with an improvement in the control of voluntary locomotion assessed by using the ladder rung test. Rats treated with Netrin-1 showed a decreased number of missed steps and slipped steps in the ladder as compared to controls. At the histology, it was observed a significant regeneration of axonal tracts at the injury site in Netrin-1 treated animals. Moreover, treated animals showed decreased axonal "die-back" upstream of the injury site, and maintained synaptic vesicles. These effects were found exclusively in treated rat.In summary, Netrin-1 administration after SCI promotes a sharp recovery of locomotor activity that was correlated with reduced axonal die back and increased axon outgrowth.