Determining Neurotrophin Gradients in Vitro To Direct Axonal Outgrowth Following Spinal Cord Injury.

Abstract

A spinal cord injury can damage neuronal connections required for both motor and sensory function. Barriers to regeneration within the central nervous system, including an absence of neurotrophic stimulation, impair the ability of injured neurons to reestablish their original circuitry. Exogenous neurotrophin administration has been shown to promote axonal regeneration and outgrowth following injury. The neurotrophins possess chemotrophic properties that guide axons toward the region of highest concentration. These growth factors have demonstrated potential to be used as a therapeutic intervention for orienting axonal growth beyond the injury lesion, toward denervated targets. However, the success of this approach is dependent on the appropriate spatiotemporal distribution of these molecules to ensure detection and navigation by the axonal growth cone. A number of in vitro gradient-based assays have been employed to investigate axonal response to neurotrophic gradients. Such platforms have helped elucidate the potential of applying a concentration gradient of neurotrophins to promote directed axonal regeneration toward a functionally significant target. Here, we review these techniques and the principles of gradient detection in axonal guidance, with particular focus on the use of neurotrophins to orient the trajectory of regenerating axons.