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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 (TNF- ), an inflammatory cytokine,
was observed in neurons and glial cells, consistent with MP regulation
of TNF- 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-
Copyright © 1999 Society for Neuroscience 0270-6474/99/19219355-09$05.00/0
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