Sex differences in the effect of progesterone after controlled cortical impact in adolescent mice: a preliminary study - PubMed (original) (raw)

Sex differences in the effect of progesterone after controlled cortical impact in adolescent mice: a preliminary study

Rebekah Mannix et al. J Neurosurg. 2014 Dec.

Abstract

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.

Keywords: CCI = controlled cortical impact; MWM = Morris water maze; TBI = traumatic brain injury; adolescent; neuroprotection; progesterone; sex differences; traumatic brain injury.

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Conflict of interest statement

The authors report no conflicts of interest

Figures

Figure 1

Figure 1

Wire grip testing after controlled cortical impact (CCI) demonstrates a protective effect in progesterone treated male mice, but a deleterious effect in progesterone treated female mice. A) Compared to vehicle treated mice, progesterone treated adolescent male mice showed improved vestibulomotor function up to 8 days after injury (p <0.001). B) Progesterone-treated adolescent female mice had worse performance on wire grip compared to vehicle treated adolescent female mice (p=0.001).

Figure 1

Figure 1

Wire grip testing after controlled cortical impact (CCI) demonstrates a protective effect in progesterone treated male mice, but a deleterious effect in progesterone treated female mice. A) Compared to vehicle treated mice, progesterone treated adolescent male mice showed improved vestibulomotor function up to 8 days after injury (p <0.001). B) Progesterone-treated adolescent female mice had worse performance on wire grip compared to vehicle treated adolescent female mice (p=0.001).

Figure 2

Figure 2

No differences in Morris water maze testing (MWM) and lesion volume after CCI and treatment. A) Compared to vehicle treated injured male mice, injured progesterone treated adolescent male mice showed no difference in hidden or visual platform trial performance (p= 0.6). B) Progesterone-treated injured adolescent female mice had similar performance on MWM compared to vehicle treated injured adolescent female mice (p=0.6). C) On lesion volume analysis, there were no differences in percent tissue lost in progesterone versus vehicle treated injured adolescent male mice or progesterone versus vehicle treated injured adolescent female mice (representative photos shown here).

Figure 2

Figure 2

No differences in Morris water maze testing (MWM) and lesion volume after CCI and treatment. A) Compared to vehicle treated injured male mice, injured progesterone treated adolescent male mice showed no difference in hidden or visual platform trial performance (p= 0.6). B) Progesterone-treated injured adolescent female mice had similar performance on MWM compared to vehicle treated injured adolescent female mice (p=0.6). C) On lesion volume analysis, there were no differences in percent tissue lost in progesterone versus vehicle treated injured adolescent male mice or progesterone versus vehicle treated injured adolescent female mice (representative photos shown here).

Figure 2

Figure 2

No differences in Morris water maze testing (MWM) and lesion volume after CCI and treatment. A) Compared to vehicle treated injured male mice, injured progesterone treated adolescent male mice showed no difference in hidden or visual platform trial performance (p= 0.6). B) Progesterone-treated injured adolescent female mice had similar performance on MWM compared to vehicle treated injured adolescent female mice (p=0.6). C) On lesion volume analysis, there were no differences in percent tissue lost in progesterone versus vehicle treated injured adolescent male mice or progesterone versus vehicle treated injured adolescent female mice (representative photos shown here).

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