title: Progesterone and vitamin D combination therapy modulates inflammatory response after traumatic brain injury.
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 vitro studies 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.
  
  
  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.
authors.affiliation: a Department of Emergency Medicine , Emory University , Atlanta , GA , USA.
authors.forename: Huiling
authors.initials: H
authors.lastname: Tang
authors.affiliation: a Department of Emergency Medicine , Emory University , Atlanta , GA , USA.
authors.forename: Fang
authors.initials: F
authors.lastname: Hua
authors.affiliation: a Department of Emergency Medicine , Emory University , Atlanta , GA , USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: a Department of Emergency Medicine , Emory University , Atlanta , GA , USA.
authors.forename: Seema
authors.initials: S
authors.lastname: Yousuf
authors.affiliation: a Department of Emergency Medicine , Emory University , Atlanta , GA , USA.
authors.forename: Fahim
authors.initials: F
authors.lastname: Atif
authors.affiliation: a Department of Emergency Medicine , Emory University , Atlanta , GA , USA.
authors.forename: Iqbal
authors.initials: I
authors.lastname: Sayeed
authors.affiliation: a Department of Emergency Medicine , Emory University , Atlanta , GA , USA.
authors.forename: Donald G
authors.initials: DG
authors.lastname: Stein
keywords: Cytokines; frontal cortex; neuroprotection; neurosteroids; toll-like receptors