Spinal cord injury (SCI) in adult rats initiates a cascade of events producing a non-permissive environment for axonal regeneration. This non-favorable environment could be due to the expression of repulsive factors like the Eph receptors and their ligands (ephrins). The Eph receptors and their respective ephrins play a major in axonal pathfinding and target recognition during ventral nervous system (CNS) development, and their action is mediated by repellent forces between receptor and ligand. The possible role that these ligands play after CNS trauma is unknown. The goal of this pilot study is to investigate the role of Ephrin B ligands in producing a non-permissive environment for axonal regeneration after SCI. Molecular biology, protein biochemistry, and neuroimaging tracing strategies will be used to analyze the expression and function of these proteins in rats injured at the T10 level..
The first aim will focus on the spatial and temporal expression of ephrin B, mRNAs and proteins, after spinal cord trauma. These experiments will provide temporal and spatial information about ephrin B expression after central nervous system (CNS) lesion at the nucleic and amino acid level. The expression pattern will be correlated both with the lack of regeneration of specific supraspinal pathways and the non-favorable regions for axonal outgrowth and circuit reconnection generated at the lesion site after moderate spinal cord contusion. In the second aim, we will determine the possible role of ephrins B as repulsive molecular cues that restrict axonal regeneration after SCI. For this study, specific polyclonal antibodies against the amino terminus of the ephrin B ligands or fusion proteins expressing the amino terminus of the ephrins B will be administered to contused rats to black the endogenous receptor-ligand interaction. Therefore, defining the specific temporal and spatial expression of individual ephrins B, both on the regenerating fibers and in the local microenvironment, may lead to novel therapeutic strategies to enhanced regeneration and functional recovery after SCI.
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