RT Journal Article
SR Electronic
T1 Glucocorticoid Regulation of Ependymal Glia and Regenerative Potential after Spinal Cord Injury
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 328781
DO 10.1101/328781
A1 Craig M. Nelson
A1 Han Lee
A1 Randall G. Krug
A1 Aichurok Kamalova
A1 Nicolas N. Madigan
A1 Karl J. Clark
A1 Vanda A. Lennon
A1 Anthony J. Windebank
A1 John R. Henley
YR 2018
UL http://biorxiv.org/content/early/2018/05/25/328781.abstract
AB Following injury, the mammalian spinal cord forms a glial scar and fails to regenerate. In contrast, spinal cord tissue of vertebrate fish regenerates and restores function. Cord transection in zebrafish (Danio rerio) initially causes paralysis and neural cell death, with subsequent ependymal glial proliferation, extension of bipolar glia across the lesion, and neurogenesis. Axons extending from spared and nascent neurons along trans-lesional glial bridges restore functional connectivity. Here we report that glucocorticoids directly target the regeneration supporting changes in ependymal glia to inhibit neural repair. This effect is independent of hematogenic immune cells or microglia. Furthermore, glucocorticoid receptor signaling in ependymal glia is inversely regulated in rat models of spinal cord injury compared to zebrafish. The blockade of neural regeneration by glucocorticoids via a direct effect on ependymal glia has important clinical implications concerning the putative therapeutic benefit of corticosteroids in early management of spinal cord injury.