One important aspect of recovery and repair after spinal cord injury (SCI) lies in
the complex cellular interactions at the injury site that leads to the formation of
a lesion scar. EphA4, a promiscuous member of the EphA family of repulsive axon guidance
receptors, is expressed by multiple cell types in the injured spinal cord, including
astrocytes and neurons. We hypothesized that EphA4 contributes to aspects of cell-cell
interactions at the injury site after SCI, thus modulating the formation of the astroglial-fibrotic
scar. To test this hypothesis, we studied tissue responses to a thoracic dorsal hemisection
SCI in an EphA4 mutant mouse line. We found that EphA4 expression, as assessed by
beta-galactosidase reporter gene activity, is associated primarily with astrocytes
in the spinal cord, neurons in the cerebral cortex and, to a lesser extent, spinal
neurons, before and after SCI. However, we did not observe any overt reduction of
glial fibrillary acidic protein (GFAP) expression in the injured area of EphA4 mutants
in comparison with controls following SCI. Furthermore, there was no evident disruption
of the fibrotic scar, and the boundary between reactive astrocytes and meningeal fibroblasts
appeared unaltered in the mutants, as were lesion size, neuronal survival and inflammation
marker expression. Thus, genetic deletion of EphA4 does not significantly alter the
astroglial response or the formation of the astroglial-fibrotic scar following a dorsal
hemisection SCI in mice. In contrast to what has been proposed, these data do not
support a major role for EphA4 in reactive astrogliosis following SCI.
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