title: Sex differences in the effect of progesterone after controlled cortical impact in adolescent mice: a preliminary study.
abstract: OBJECTIVE
  While progesterone has been well studied in experimental models of adult traumatic brain injury (TBI), it has not been evaluated in pediatric models. The study of promising interventions in pediatric TBI is important because children have the highest public health burden of such injuries. Therapies that are beneficial in adults may not necessarily be effective in the pediatric population. The purpose of this study was to evaluate whether progesterone treatment improves outcomes in an experimental model of pediatric TBI.
  
  
  METHODS
  The authors determined whether progesterone administered after controlled cortical impact (CCI) improves functional and histopathological outcomes in 4-week-old mice. Both male and female mice (58 mice total) were included in this study, as the majority of prior studies have used only male and/or reproductively senescent females. Mice were randomized to treatment with progesterone or vehicle and to CCI injury or sham injury. Motor (wire grip test) and memory (Morris water maze) testing were performed to determine the effect of progesterone on TBI. Lesion volume was also assessed.
  
  
  RESULTS
  Compared with their vehicle-treated counterparts, the progesterone-treated CCI-injured male mice had improved motor performance (p < 0.001). In contrast, progesterone-treated CCI-injured female mice had a worse performance than their vehicle-treated counterparts (p = 0.001). Progesterone treatment had no effect on spatial memory performance or lesion volume in injured male or female mice.
  
  
  CONCLUSIONS
  These data suggest a sex-specific effect of progesterone treatment after CCI in adolescent mice and could inform clinical trials in children.
authors.affiliation: Division of Emergency Medicine.
authors.forename: Rebekah
authors.initials: R
authors.lastname: Mannix
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Berglass
authors.forename: Justin
authors.initials: J
authors.lastname: Berkner
authors.forename: Philippe
authors.initials: P
authors.lastname: Moleus
authors.forename: Jianhua
authors.initials: J
authors.lastname: Qiu
authors.forename: Lauren L
authors.initials: LL
authors.lastname: Jantzie
authors.forename: William P
authors.initials: WP
authors.lastname: Meehan
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Stanley
authors.forename: Shenandoah
authors.initials: S
authors.lastname: Robinson
mesh_terms: D000367:Age Factors; D000818:Animals; D001930:Brain Injuries / Q000188:drug therapy*; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D010865:Pilot Projects; D011374:Progesterone / Q000494:pharmacology*; D011372:Progestins / Q000494:pharmacology; D011897:Random Allocation; D020127:Recovery of Function / Q000187:drug effects*; D012727:Sex Characteristics; D065852:Spatial Memory / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D011372:Progestins; D011374:Progesterone
keywords: CCI = controlled cortical impact; MWM = Morris water maze; TBI = traumatic brain injury; adolescent; neuroprotection; progesterone; sex differences; traumatic brain injury