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Journal of neurosurgery · Dec 2014
Sex differences in the effect of progesterone after controlled cortical impact in adolescent mice: a preliminary study.
- Rebekah Mannix, Jacqueline Berglass, Justin Berkner, Philippe Moleus, Jianhua Qiu, Lauren L Jantzie, William P Meehan, Rachel M Stanley, and Shenandoah Robinson.
- Division of Emergency Medicine.
- J. Neurosurg. 2014 Dec 1; 121 (6): 1337-41.
ObjectWhile 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.MethodsThe 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.ResultsCompared 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.ConclusionsThese data suggest a sex-specific effect of progesterone treatment after CCI in adolescent mice and could inform clinical trials in children.
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