1. Progesterone and vitamin D combination therapy modulates inflammatory response after traumatic brain injury.
- Author
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Tang, Huiling, Hua, Fang, Wang, Jun, Yousuf, Seema, Atif, Fahim, Sayeed, Iqbal, and Stein, Donald G.
- Subjects
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ANIMAL experimentation , *BIOLOGICAL models , *BRAIN injuries , *CELL receptors , *CELLULAR signal transduction , *COMBINATION drug therapy , *CYTOKINES , *ENZYME-linked immunosorbent assay , *FRONTAL lobe , *IMMUNOHISTOCHEMISTRY , *INFLAMMATION , *NEURONS , *HEALTH outcome assessment , *PHOSPHORYLATION , *PROBABILITY theory , *PROGESTERONE , *RATS , *RESEARCH funding , *STATISTICS , *VITAMIN D , *WESTERN immunoblotting , *MICROTECHNIQUE , *DATA analysis , *NEURAL pathways , *DATA analysis software , *DESCRIPTIVE statistics , *ONE-way analysis of variance - Abstract
Objective: Inflammation is an important component of the response to traumatic brain injury (TBI). Progesterone has been shown to inhibit neuroinflammation following (TBI) and may do so through Toll-like receptor (TLR)-mediated pathways.In vitrostudies indicate that 1,25-dihydroxyvitamin D(3) (VDH) may also modulate the inflammatory response through the TLR4 pathway. This study tested the hypothesis that PROG and VDH would exert additive and synergistic neuroprotective effects compared with individual treatment by modulating TLR4/NF-κB-mediated inflammation pathways after TBI in rats. Research design and methods: Bilateral medial frontal cortical impact injury was induced in young adult Sprague-Dawley rats. Progesterone (i.p., 16 mg kg−1body weight) and VDH (1 µg kg−1body weight) were injected separately or combined at 1 and 6 hours after surgery. Rats were killed 24 hours post-surgery and peri-contusional brain tissue harvested for immunostaining and protein measurement. Results: TLR4, phosphorylation of NF-κB, neuronal loss and astrocyte activation were significantly reduced with combination treatment after TBI compared to each agent given individually. Conclusions: At 24 hours after TBI, combination therapy shows greater efficacy in reducing neuroinflammation compared to progesterone and VDH given separately, and does so by modulating the TLR4/NF-κB signalling pathway. [ABSTRACT FROM PUBLISHER]
- Published
- 2015
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