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.
Conflict of interest statement
The authors report no conflicts of interest
Figures
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
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
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
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
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).
Similar articles
- Conjugated Linoleic Acid Administration Induces Amnesia in Male Sprague Dawley Rats and Exacerbates Recovery from Functional Deficits Induced by a Controlled Cortical Impact Injury.
Geddes RI, Hayashi K, Bongers Q, Wehber M, Anderson IM, Jansen AD, Nier C, Fares E, Farquhar G, Kapoor A, Ziegler TE, VadakkadathMeethal S, Bird IM, Atwood CS. Geddes RI, et al. PLoS One. 2017 Jan 26;12(1):e0169494. doi: 10.1371/journal.pone.0169494. eCollection 2017. PLoS One. 2017. PMID: 28125600 Free PMC article. - Gender associations with chronic methylphenidate treatment and behavioral performance following experimental traumatic brain injury.
Wagner AK, Kline AE, Ren D, Willard LA, Wenger MK, Zafonte RD, Dixon CE. Wagner AK, et al. Behav Brain Res. 2007 Aug 6;181(2):200-9. doi: 10.1016/j.bbr.2007.04.006. Epub 2007 Apr 20. Behav Brain Res. 2007. PMID: 17517440 Free PMC article. - Detrimental effect of genetic inhibition of B-site APP-cleaving enzyme 1 on functional outcome after controlled cortical impact in young adult mice.
Mannix RC, Zhang J, Park J, Lee C, Whalen MJ. Mannix RC, et al. J Neurotrauma. 2011 Sep;28(9):1855-61. doi: 10.1089/neu.2011.1759. Epub 2011 Aug 29. J Neurotrauma. 2011. PMID: 21639727 Free PMC article. - Progesterone for neuroprotection in pediatric traumatic brain injury.
Robertson CL, Fidan E, Stanley RM, Noje C, Bayir H. Robertson CL, et al. Pediatr Crit Care Med. 2015 Mar;16(3):236-44. doi: 10.1097/PCC.0000000000000323. Pediatr Crit Care Med. 2015. PMID: 25581631 Free PMC article. Review. - Elucidating opportunities and pitfalls in the treatment of experimental traumatic brain injury to optimize and facilitate clinical translation.
de la Tremblaye PB, O'Neil DA, LaPorte MJ, Cheng JP, Beitchman JA, Thomas TC, Bondi CO, Kline AE. de la Tremblaye PB, et al. Neurosci Biobehav Rev. 2018 Feb;85:160-175. doi: 10.1016/j.neubiorev.2017.05.022. Epub 2017 May 30. Neurosci Biobehav Rev. 2018. PMID: 28576511 Free PMC article. Review.
Cited by
- Reactive oxygen species-responsive HET0016 prodrug-loaded liposomes attenuate neuroinflammation and improve neurological deficit in a rat model of juvenile traumatic brain injury.
Qin J, Chen X, Wang R, Tian Z, Li Y, Shu S. Qin J, et al. Front Neurosci. 2023 Mar 22;17:1153349. doi: 10.3389/fnins.2023.1153349. eCollection 2023. Front Neurosci. 2023. PMID: 37034179 Free PMC article. - Importance of Control Groups for Evaluating Long-Term Behavioral and Cognitive Outcomes of Controlled Cortical Impact in Immature Rats.
El-Demerdash N, Pan T, Choi O, Saraswati M, Koehler RC, Robertson CL, Savonenko A. El-Demerdash N, et al. J Neurotrauma. 2023 Jun;40(11-12):1197-1215. doi: 10.1089/neu.2021.0376. Epub 2023 Mar 1. J Neurotrauma. 2023. PMID: 36416234 Free PMC article. - Effects of Progesterone on Preclinical Animal Models of Traumatic Brain Injury: Systematic Review and Meta-analysis.
Nasre-Nasser RG, Severo MMR, Pires GN, Hort MA, Arbo BD. Nasre-Nasser RG, et al. Mol Neurobiol. 2022 Oct;59(10):6341-6362. doi: 10.1007/s12035-022-02970-9. Epub 2022 Aug 4. Mol Neurobiol. 2022. PMID: 35922729 - A Pro-social Pill? The Potential of Pharmacological Treatments to Improve Social Outcomes After Pediatric Traumatic Brain Injury.
Semple BD, Raghupathi R. Semple BD, et al. Front Neurol. 2021 Aug 19;12:714253. doi: 10.3389/fneur.2021.714253. eCollection 2021. Front Neurol. 2021. PMID: 34489853 Free PMC article. Review. - The sex-specific interaction of the microbiome in neurodegenerative diseases.
Cox LM, Abou-El-Hassan H, Maghzi AH, Vincentini J, Weiner HL. Cox LM, et al. Brain Res. 2019 Dec 1;1724:146385. doi: 10.1016/j.brainres.2019.146385. Epub 2019 Aug 13. Brain Res. 2019. PMID: 31419428 Free PMC article. Review.
References
- Adelson PD, Whalen MJ, Kochanek PM, Robichaud P, Carlos TM. Blood brain barrier permeability and acute inflammation in two models of traumatic brain injury in the immature rat: a preliminary report. Acta Neurochir Suppl. 1998;71:104–106. - PubMed
- Behl C, Trapp T, Skutella T, Holsboer F. Protection against oxidative stress-induced neuronal cell death--a novel role for RU486. Eur J Neurosci. 1997;9:912–920. - PubMed
- Clark RS, Kochanek PM, Schwarz MA, Schiding JK, Turner DS, Chen M, et al. Inducible nitric oxide synthase expression in cerebrovascular smooth muscle and neutrophils after traumatic brain injury in immature rats. Pediatr Res. 1996;39:784–790. - PubMed
- Concas A, Follesa P, Barbaccia ML, Purdy RH, Biggio G. Physiological modulation of GABA(A) receptor plasticity by progesterone metabolites. Eur J Pharmacol. 1999;375:225–235. - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources