Induction of Eph B3 after spinal cord injury

Spinal cord injury (SCI) in adult rats initiates a cascade of events produc ing a nonpermissive environment for axonal regeneration. This nonfavorable environment could be due to the expression of repulsive factors. The Eph re ceptor protein tyrosine kinases and their respective ligands (ephrins) are families of molecules that play a major role in axonal pathfinding and targ et recognition during central nervous system (CNS) development. Their mecha nism of action is mediated by repellent forces between receptor and ligand. The possible role that these molecules play after CNS trauma is unknown. W e hypothesized that an increase in the expression of Eph proteins and/or ep hrins may be one of the molecular cues that restrict axonal regeneration af ter SCI. Rats received a contusive SCI at T10 and in situ hybridization stu dies 7 days posttrauma demonstrated: (i) a marked up-regulation of Eph B3 m RNA in cells located in the white matter at the lesion epicenter, but not r ostral or caudal to the injury site, and (ii) an increase in Eph B3 mRNA in neurons in the ventral horn and intermediate zone of the gray matter, rost ral and caudal to the lesion. Immunohistochemical analyses localizing Eph B 3 protein were consistent with the mRNA results. Colocalization studies per formed in injured animals demonstrated increased Eph B3 expression in white matter astrocytes and motor neurons of the gray matter. These results sugg est that Eph B3 may contribute to the unfavorable environment for axonal re generation after SCI. (C) 1999 Academic Press.