Regeneración y reconexión neuronal en lesiones de médula espinal: Una aproximación desde la ciencia básica

H.R QUINTÁ

Otro; Ateneo de clínica médica - Hospital Alemán; 2022

In traumatic spinal cord injury (SCI), the fluxof information along the shaft of long motor and sensory spinal axons isinterrupted. Therefore the goal for overcome the deleterious effect produced bythis pathology is to promote re-growth of the damage spinal axons as well as aneffective re-connection of its with the lower neuronal targets to achieve arecovery of locomotor functions.According tothis background, this research is focus in the design of therapeutic approach tothis traumatic pathology. Netrin-1, an axonal chemoattractant protein, isinvolved in axonal growth during the embryonic development. This protein drivesthe corticospinal axons growth and its navigation across the pyramidaldecussation to the lowest part of spinal cord by a haptotaxis phenomenon.As was described previously, Netrin-1 treatmentpromotes a significant recovery of locomotor activity in rats with a completeSCI at thoracic level 10, assessed by using BBB score. Moreover, this result correlatedwith an improvement in the control of voluntary locomotion assessed with the ladderrung test. Rats treated with Netrin-1 showed a decreased number of missed stepsand slipped steps in the ladder compared to controls. In line withthis, a stereotaxic surgery was carried out to trace the corticospinal axons.Using “clearing technique” it was observed a significant regeneration of corticospinalaxons at the lesion site only in Netrin-1 treated animals, as well as asignificant maintaining in the number of synaptic contact downstream of lesionsite. Besides, in-vivo trans-synaptic interaction was demonstrated only in ratstreated with Netrin-1. In conclusion, Netrin-1 administration in acuteSCI promotes regeneration of corticospinal axons, prevents the dying back inthe sensitive axonal shaft structure, stimulated the neo-formation and re-arrangementof synaptic contact and spinal tissue preservation. All of these cellular processescould partially explain the pathway by which Netrin-1 treatment significant recoverthe locomotor function after injury.