Glucocorticoid receptor expression in the spinal cord after traumatic injury in adult rats.
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.
Yan
P
P
Department of Anatomy, St. Louis University School of Medicine, St. Louis, Missouri 63104, USA.
Xu
J
J
Li
Q
Q
Chen
S
S
Kim
G M
GM
Hsu
C Y
CY
Xu
X M
XM
D000818:Animals; D001369:Axons / Q000378:metabolism; D003712:Dendrites / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D008959:Models, Neurological; D009411:Nerve Endings / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D020318:Rats, Long-Evans; D011965:Receptors, Glucocorticoid / Q000032:analysis / Q000235:genetics*; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000235:genetics
D011965:Receptors, Glucocorticoid; D014409:Tumor Necrosis Factor-alpha