Glucocorticoid receptor expression in the spinal cord after traumatic injury in adult rats

Methylprednisolone (MP), a glucocorticoid, is the only effective therapeuti c agent used in the clinical treatment of acute spinal cord injury (SCI). M P given within 8 hr after SCI significantly improves neurological function. Although the glucocorticoid receptor (GR) is suggested to mediate MP actio ns, limited knowledge is available on its expression and possible function after SCI. Presently, the expression of GR was studied in a weight-drop SCI model in adult rats. Immunohistochemistry and Western blot analysis reveal ed an increase in GR protein expression as early as 15 min after injury. GR expression sharply increased at 4 hr (22-fold), peaked at 8 hr (56-fold), rapidly declined at 1 d, and returned to the baseline level at and after 3 d. During its peak expression, GR was localized in neural somata and dendri tes but not in axons and their terminals. GR immunoreactivity was also foun d in oligodendrocytes and astrocytes. Interestingly, other cell types, such as endothelial cells, were GR-negative. An increase in the binding activit y of nuclear proteins to the glucocorticoid responsive element was also obs erved after SCI, demonstrating a functional element of GR activation. Final ly, colocalization of GR and tumor necrosis factor alpha (TNF-alpha), an in flammatory cytokine, was observed in neurons and glial cells, consistent wi th MP regulation of TNF-alpha in this model. Thus, the transient expression of high levels of GR after SCI may provide new insights into the antiinfla mmatory action of MP.