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B Signaling Pathway in Rat Brain after Cortical ContusionAddress 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-
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-
B binding activity by electrophoretic mobility shift assay (EMSA), concentrations of interleukin-1β (IL-1β), tumor necrosis factor-
(TNF-
), 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-
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-
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-
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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