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Annals of Clinical & Laboratory Science 38:65-74 (2008)
© 2008 Association of Clinical Scientists

Progesterone Administration Modulates TLRs/NF-{kappa}B Signaling Pathway in Rat Brain after Cortical Contusion

Gang Chen1, Jixin Shi1, Wei Jin1, Lin Wang1, Weiying Xie2, Jie Sun2 and Chunhua Hang1
1 Departments of Neurosurgery and 2 Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, China

Address correspondence to Chunhua Hang, M.D., Dept. of Neurosurgery, Jinling Hospital, 305 East Zhongshan Road, Nanjing 210002, P.R.China; tel 86 25 8197 3916; fax 86 25 8481 7581; email nju_neurosurgery{at}163.com.

This study investigated whether progesterone administration modulates toll-like receptors (TLRs) and the nuclear factor-kappa B (NF-{kappa}B) signaling pathway in the injured rat brain following traumatic brain injury (TBI). Right parietal cortical contusion was made by a weight-dropping method. Male rats were given 0 or 16 mg/kg injections of progesterone at postinjury hr 1 and 6 and on days 1, 2, 3, 4, and 5. Brain samples were extracted at 5 days after trauma. We measured mRNA expression of TLR2 and TLR4 by reverse-transcriptase polymerase chain reaction (RT-PCR), NF-{kappa}B binding activity by electrophoretic mobility shift assay (EMSA), concentrations of interleukin-1β (IL-1β), tumor necrosis factor-{alpha} (TNF-{alpha}), and interleukin-6 (IL-6) by enzyme-linked immunosorbent assay (ELISA), intercellular adhesion molecule-1 (ICAM-1) expression by immunohistochemistry, and brain damage by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL). The results showed that TBI induces strong up-regulation of TLR2, TLR4, NF-{kappa}B, pro-inflammatory cytokines, and ICAM-1 in the pericontusional area. Administration of progesterone following TBI down-regulates the cortical levels of these agents related to the TLRs/NF-{kappa}B signaling pathway. After progesterone administration, apoptotic TUNEL-positive cells in the injured brain were significantly decreased. In summary, post-TBI progesterone administration attenuates the TLRs/NF-{kappa}B signaling pathway in injured rat brain, and this may be a mechanism whereby progesterone improves the outcome following TBI.

Keywords: progesterone, traumatic brain injury, toll-like receptors, nuclear factor-kappaB







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