Axonal regeneration in acute spinal cord injury.

HR QUINTÁ

Cordoba, Argentina

Simposio; Current Advances on Neurodegeneration: From Molecular Biology to Translational Medicine; 2017

Spinal cord injury (SCI), a traumatic pathology which affects the central nervous system, produces devastating changes often permanent in normal locomotor, sensory and autonomic function in the affected individuals. Despite extensive research in the field, the development of a successful therapeutical intervention for patients suffering this traumatic pathology remains one of the major challenges in biomedicine. The pathological process that follows a traumatic injury to the spinal cord involves the interplay of several factors, including different matricellular proteins and pro-inflammatory cytokines. Semaphorin3A (Sema3A) secreted by meningeal fibroblasts that migrate to the injury site is one of the principal inhibitory proteins inducing axonal collapse and preventing regeneration following SCI. During neuronal development, directed axonal growth in the spinal cord is crucial to establish a normal range of motor behaviors such as locomotor coordination involved in reaching and grasping tasks. Sema3A functions as a repulsive guidance cue for subsets of axons expressing the neuronal receptor complex neuropilin-1 (NRP-1)/PlexinA4. Sema3A expression in adult intact spinal cord is barely detectable. However its levels increase considerably after injury and contribute to inadequate axonal regeneration. Concomitantly, descendent motor tracts and neighboring neurons express NRP-1 and PlexinA4, rendering them susceptible to Sema3A-induced collapse. Binding of Sema3A to the neuronal receptor complex leads to intracellular signaling events that promote an increase in intra-axonal hydrogen peroxide production, which in turn oxidizes F-actin at methionine residues, resulting in F-actin destabilization and subsequent collapse of the growth cone of the injured axon. Therefore, strategies aimed at disrupting signaling downstream Sema3A may lead to axonal regeneration and functional recovery after SCI. We have shown that Galectin-1 (Gal-1), a member of a highly conserved family of animal lectins, promotes the interruption of Sema3A signaling pathway. Here the molecular basis by which the in situ treatment whit exogenous Gal-1 in an in vivo murine model contributes to promote full axonal regeneration and recovery of locomotor function after acute SCI are discussed.