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The Journal of Neuroscience, November 1, 1999, 19(21):9355-9363

Glucocorticoid Receptor Expression in the Spinal Cord after Traumatic Injury in Adult Rats

Ping Yan1, Jian Xu2, Qun Li1, 2, Sawei Chen2, Gyeong-Moon Kim2, Chung Y. Hsu2, and Xiao Ming Xu1

1 Department of Anatomy and Neurobiology, St. Louis University School of Medicine, St. Louis, Missouri 63104, and 2 Department of Neurology, Washington University School of Medicine, St. Louis, Missouri 63110

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 alpha  (TNF-alpha ), an inflammatory cytokine, was observed in neurons and glial cells, consistent with 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 anti-inflammatory action of MP.

Key words: glucocorticoid receptor; inflammation; methylprednisolone; rat; spinal cord injury; TNF-alpha


Copyright © 1999 Society for Neuroscience  0270-6474/99/19219355-09$05.00/0


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