title: EphA4 deficient mice maintain astroglial-fibrotic scar formation after spinal cord injury.
abstract: 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.
authors.affiliation: Department of Neurosciences, University of California San Diego, School of Medicine, 9500 Gilman Drive, MC 0691, La Jolla, CA 92093-0691, USA.
authors.forename: Julia E
authors.initials: JE
authors.lastname: Herrmann
authors.forename: Ravi R
authors.initials: RR
authors.lastname: Shah
authors.forename: Andrea F
authors.initials: AF
authors.lastname: Chan
authors.forename: Binhai
authors.initials: B
authors.lastname: Zheng
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000473:pathology* / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D002921:Cicatrix / Q000473:pathology* / Q000503:physiopathology; D005260:Female; D005353:Fibronectins / Q000235:genetics; D005355:Fibrosis; D015870:Gene Expression / Q000502:physiology; D017930:Genes, Reporter; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics; D005911:Gliosis / Q000473:pathology / Q000503:physiopathology; D008578:Meninges / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009187:Myelitis / Q000473:pathology* / Q000503:physiopathology; D009416:Nerve Regeneration / Q000502:physiology; D009474:Neurons / Q000473:pathology / Q000502:physiology; D036122:Receptor, EphA4 / Q000235:genetics* / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000473:pathology* / Q000503:physiopathology; D001616:beta-Galactosidase / Q000235:genetics
chemical_list: D005353:Fibronectins; D005904:Glial Fibrillary Acidic Protein; D036122:Receptor, EphA4; D001616:beta-Galactosidase