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Sex differences in the effect of progesterone after controlled cortical impact in adolescent mice: a preliminary
Rebekah Mannix1, Jacqueline Berglass, Justin Berkner
1Division of Emergency Medicine.
Insights
Progesterone improved motor function in male mice after traumatic brain injury (TBI) but worsened it in females. This sex-specific effect in pediatric TBI models suggests careful consideration for clinical trials.
Area of Science:
- Neuroscience
- Pediatric Traumatology
Background:
- Progesterone's therapeutic potential in adult traumatic brain injury (TBI) is established, yet its efficacy in pediatric TBI remains unevaluated.
- Pediatric TBI presents a significant public health challenge, necessitating research into age-specific treatments.
- Interventions effective in adults may not translate to pediatric populations due to developmental differences.
Purpose of the Study:
- To investigate the effects of progesterone on functional and histopathological outcomes in an experimental model of pediatric TBI.
- To determine if progesterone administration post-injury improves outcomes in adolescent mice.
Main Methods:
- Controlled cortical impact (CCI) was induced in 4-week-old male and female mice.
- Mice were randomized to receive either progesterone or vehicle treatment.
- Functional assessments included motor (wire grip test) and memory (Morris water maze) tests, alongside lesion volume analysis.
Main Results:
- Progesterone treatment significantly improved motor performance in male mice post-CCI compared to vehicle controls (p < 0.001).
- Conversely, progesterone treatment worsened motor performance in female mice post-CCI (p = 0.001).
- No significant effects of progesterone were observed on spatial memory or lesion volume in either sex.
Conclusions:
- The findings indicate a sex-specific response to progesterone treatment following CCI in adolescent mice.
- These results highlight the need to consider sex as a biological variable in pediatric TBI research.
- The study's outcomes may inform the design of future clinical trials for pediatric TBI.
Object:
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.
