Corticospinal axons reconnection promotes the recovery of voluntary locomotion after acute Spinal Cord Injury

SCHMIDT, JULIETA; H.R QUINTÁ

Congreso; Sociedad Argentina de Investigación Clínica; 2022

SAIC

In traumatic spinal cord injury (SCI), the fluxof information along the shaft of long motor and sensory spinal axons is interrupted.The goal is to overcome the deleterious effect produced by SCI promotingre-growth of the damage axons as well as a functional re-connection of its withthe lower neuronal targets to achieve a recovery of locomotor functions.According to this, the aim of this research isfocused in the design of a therapeutic approach in SCI.Netrin-1, a chemoattractant protein, isinvolved in axonal growth during the embryonic development. Netrin-1 drives thecorticospinal axons growth and its navigation across the pyramidal decussationto the white matter spinal cord by a haptotaxis phenomenon.As I previously described, Netrin-1 promotes asignificant recovery of locomotor activity in rats with a complete SCI at Th10level, assessed by BBB score. Furthermore, this result correlates with asignificant improvement in the control of voluntary locomotion, assessed by ladder rung test. In line with this, a stereotaxic surgery wascarried out to trace the corticospinal axons. Using the clearing technique itwas observed a significant regeneration of corticospinal axons at the lesionsite only in Netrin-1 treated rats, as well as a significant preservation inthe number of synaptic contacts downstream of the lesion. Besides, an in-vivotrans-synaptic interaction was revealed only in treated rats. Finally, using a 3-Tesla MRI, a preservation ofmyelinated spinal tissue was shown in Netrin-1 treated rats after SCI.In conclusion, the administration of Netrin-1 inacute SCI promotes regeneration of corticospinal axons, prevents axonal dyingback, stimulates neo-formation and re-arrangement of synaptic contacts and preservesthe myelinated spinal tissue. All of these cellular processes could partiallyexplain the pathway by which Netrin-1 addition produces a significant recoveryof locomotor function after injury.