Methylprednisolone (MP), a glucocorticoid, is the only effective therapeutic agent used in the clinical treatment of acute spinal cord injury (SCI). MP given within 8 hr after SCI significantly improves neurological function. Although the glucocorticoid receptor (GR) is suggested to mediate MP actions, 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 revealed 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 dendrites but not in axons and their terminals. GR immunoreactivity was also found in oligodendrocytes and astrocytes. Interestingly, other cell types, such as endothelial cells, were GR-negative. An increase in the binding activity of nuclear proteins to the glucocorticoid responsive element was also observed after SCI, demonstrating a functional element of GR activation. Finally, colocalization of GR and tumor necrosis factor α (TNF-α), an inflammatory cytokine, was observed in neurons and glial cells, consistent with MP regulation of TNF-α in this model. Thus, the transient expression of high levels of GR after SCI may provide new insights into the anti- inflammatory action of MP.
|Original language||English (US)|
|Number of pages||9|
|Journal||Journal of Neuroscience|
|State||Published - Nov 1 1999|
- Glucocorticoid receptor
- Spinal cord injury
ASJC Scopus subject areas