Progesterone Treatment Shows Benefit in Female Rats in a Pediatric Model of Controlled Cortical Impact Injury

We recently showed that progesterone treatment can reduce lesion size and behavioral deficits after moderate-to-severe bilateral injury to the medial prefrontal cortex in immature male rats. Whether there are important sex differences in response to injury and progesterone treatment in very young su...

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Published inPloS one Vol. 11; no. 1; p. e0146419
Main Authors Geddes, Rastafa I., Peterson, Bethany L., Stein, Donald G., Sayeed, Iqbal
Format Journal Article
LanguageEnglish
Published United States Public Library of Science 22.01.2016
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Abstract We recently showed that progesterone treatment can reduce lesion size and behavioral deficits after moderate-to-severe bilateral injury to the medial prefrontal cortex in immature male rats. Whether there are important sex differences in response to injury and progesterone treatment in very young subjects has not been given sufficient attention. Here we investigated progesterone's effects in the same model of brain injury but with pre-pubescent females. Twenty-eight-day-old female Sprague-Dawley rats received sham (n = 14) or controlled cortical impact (CCI) (n = 21) injury, were given progesterone (8 mg/kg body weight) or vehicle injections on post-injury days (PID) 1-7, and underwent behavioral testing from PID 9-27. Brains were evaluated for lesion size at PID 28. Lesion size in vehicle-treated female rats with CCI injury was smaller than that previously reported for similarly treated age-matched male rats. Treatment with progesterone reduced the effect of CCI on extent of damage and behavioral deficits. Pre-pubescent female rats with midline CCI injury to the frontal cortex have reduced morphological and functional deficits following progesterone treatment. While gender differences in susceptibility to this injury were observed, progesterone treatment produced beneficial effects in young rats of both sexes following CCI.
AbstractList Purpose We recently showed that progesterone treatment can reduce lesion size and behavioral deficits after moderate-to-severe bilateral injury to the medial prefrontal cortex in immature male rats. Whether there are important sex differences in response to injury and progesterone treatment in very young subjects has not been given sufficient attention. Here we investigated progesterone's effects in the same model of brain injury but with pre-pubescent females. Methods Twenty-eight-day-old female Sprague-Dawley rats received sham (n = 14) or controlled cortical impact (CCI) (n = 21) injury, were given progesterone (8 mg/kg body weight) or vehicle injections on post-injury days (PID) 1-7, and underwent behavioral testing from PID 9-27. Brains were evaluated for lesion size at PID 28. Results Lesion size in vehicle-treated female rats with CCI injury was smaller than that previously reported for similarly treated age-matched male rats. Treatment with progesterone reduced the effect of CCI on extent of damage and behavioral deficits. Conclusion Pre-pubescent female rats with midline CCI injury to the frontal cortex have reduced morphological and functional deficits following progesterone treatment. While gender differences in susceptibility to this injury were observed, progesterone treatment produced beneficial effects in young rats of both sexes following CCI.
We recently showed that progesterone treatment can reduce lesion size and behavioral deficits after moderate-to-severe bilateral injury to the medial prefrontal cortex in immature male rats. Whether there are important sex differences in response to injury and progesterone treatment in very young subjects has not been given sufficient attention. Here we investigated progesterone's effects in the same model of brain injury but with pre-pubescent females. Twenty-eight-day-old female Sprague-Dawley rats received sham (n = 14) or controlled cortical impact (CCI) (n = 21) injury, were given progesterone (8 mg/kg body weight) or vehicle injections on post-injury days (PID) 1-7, and underwent behavioral testing from PID 9-27. Brains were evaluated for lesion size at PID 28. Lesion size in vehicle-treated female rats with CCI injury was smaller than that previously reported for similarly treated age-matched male rats. Treatment with progesterone reduced the effect of CCI on extent of damage and behavioral deficits. Pre-pubescent female rats with midline CCI injury to the frontal cortex have reduced morphological and functional deficits following progesterone treatment. While gender differences in susceptibility to this injury were observed, progesterone treatment produced beneficial effects in young rats of both sexes following CCI.
We recently showed that progesterone treatment can reduce lesion size and behavioral deficits after moderate-to-severe bilateral injury to the medial prefrontal cortex in immature male rats. Whether there are important sex differences in response to injury and progesterone treatment in very young subjects has not been given sufficient attention. Here we investigated progesterone's effects in the same model of brain injury but with pre-pubescent females.PURPOSEWe recently showed that progesterone treatment can reduce lesion size and behavioral deficits after moderate-to-severe bilateral injury to the medial prefrontal cortex in immature male rats. Whether there are important sex differences in response to injury and progesterone treatment in very young subjects has not been given sufficient attention. Here we investigated progesterone's effects in the same model of brain injury but with pre-pubescent females.Twenty-eight-day-old female Sprague-Dawley rats received sham (n = 14) or controlled cortical impact (CCI) (n = 21) injury, were given progesterone (8 mg/kg body weight) or vehicle injections on post-injury days (PID) 1-7, and underwent behavioral testing from PID 9-27. Brains were evaluated for lesion size at PID 28.METHODSTwenty-eight-day-old female Sprague-Dawley rats received sham (n = 14) or controlled cortical impact (CCI) (n = 21) injury, were given progesterone (8 mg/kg body weight) or vehicle injections on post-injury days (PID) 1-7, and underwent behavioral testing from PID 9-27. Brains were evaluated for lesion size at PID 28.Lesion size in vehicle-treated female rats with CCI injury was smaller than that previously reported for similarly treated age-matched male rats. Treatment with progesterone reduced the effect of CCI on extent of damage and behavioral deficits.RESULTSLesion size in vehicle-treated female rats with CCI injury was smaller than that previously reported for similarly treated age-matched male rats. Treatment with progesterone reduced the effect of CCI on extent of damage and behavioral deficits.Pre-pubescent female rats with midline CCI injury to the frontal cortex have reduced morphological and functional deficits following progesterone treatment. While gender differences in susceptibility to this injury were observed, progesterone treatment produced beneficial effects in young rats of both sexes following CCI.CONCLUSIONPre-pubescent female rats with midline CCI injury to the frontal cortex have reduced morphological and functional deficits following progesterone treatment. While gender differences in susceptibility to this injury were observed, progesterone treatment produced beneficial effects in young rats of both sexes following CCI.
We recently showed that progesterone treatment can reduce lesion size and behavioral deficits after moderate-to-severe bilateral injury to the medial prefrontal cortex in immature male rats. Whether there are important sex differences in response to injury and progesterone treatment in very young subjects has not been given sufficient attention. Here we investigated progesterone's effects in the same model of brain injury but with pre-pubescent females. Twenty-eight-day-old female Sprague-Dawley rats received sham (n = 14) or controlled cortical impact (CCI) (n = 21) injury, were given progesterone (8 mg/kg body weight) or vehicle injections on post-injury days (PID) 1-7, and underwent behavioral testing from PID 9-27. Brains were evaluated for lesion size at PID 28. Lesion size in vehicle-treated female rats with CCI injury was smaller than that previously reported for similarly treated age-matched male rats. Treatment with progesterone reduced the effect of CCI on extent of damage and behavioral deficits. Pre-pubescent female rats with midline CCI injury to the frontal cortex have reduced morphological and functional deficits following progesterone treatment. While gender differences in susceptibility to this injury were observed, progesterone treatment produced beneficial effects in young rats of both sexes following CCI.
Purpose We recently showed that progesterone treatment can reduce lesion size and behavioral deficits after moderate-to-severe bilateral injury to the medial prefrontal cortex in immature male rats. Whether there are important sex differences in response to injury and progesterone treatment in very young subjects has not been given sufficient attention. Here we investigated progesterone’s effects in the same model of brain injury but with pre-pubescent females. Methods Twenty-eight-day-old female Sprague-Dawley rats received sham (n = 14) or controlled cortical impact (CCI) (n = 21) injury, were given progesterone (8 mg/kg body weight) or vehicle injections on post-injury days (PID) 1–7, and underwent behavioral testing from PID 9–27. Brains were evaluated for lesion size at PID 28. Results Lesion size in vehicle-treated female rats with CCI injury was smaller than that previously reported for similarly treated age-matched male rats. Treatment with progesterone reduced the effect of CCI on extent of damage and behavioral deficits. Conclusion Pre-pubescent female rats with midline CCI injury to the frontal cortex have reduced morphological and functional deficits following progesterone treatment. While gender differences in susceptibility to this injury were observed, progesterone treatment produced beneficial effects in young rats of both sexes following CCI.
Audience Academic
Author Sayeed, Iqbal
Geddes, Rastafa I.
Peterson, Bethany L.
Stein, Donald G.
AuthorAffiliation Brock University, CANADA
Department of Emergency Medicine, Emory University, Atlanta, GA 30322 United States of America
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/26799561$$D View this record in MEDLINE/PubMed
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2016 Geddes et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
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Conceived and designed the experiments: RIG IS DGS. Performed the experiments: RIG BLP. Analyzed the data: RIG IS DGS. Wrote the paper: RIG DGS IS BLP.
Competing Interests: These unrestricted gifts made through the Emory Development Office do not alter the authors' adherence to PLOS ONE policies on sharing data and materials. DGS and IS hold the following patents: Methods for the treatment of a traumatic central nervous system injury, No. EP2030622B1, date approved: 2/23/2011, Method for the treatment of a traumatic central nervous system injury via a tapered administration of progesterone, No. 1871382, date approved: 8/17/2011. They do not have any licensing agreements pertaining to the patents and having the patents does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.
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Snippet We recently showed that progesterone treatment can reduce lesion size and behavioral deficits after moderate-to-severe bilateral injury to the medial...
Purpose We recently showed that progesterone treatment can reduce lesion size and behavioral deficits after moderate-to-severe bilateral injury to the medial...
PURPOSE:We recently showed that progesterone treatment can reduce lesion size and behavioral deficits after moderate-to-severe bilateral injury to the medial...
Purpose We recently showed that progesterone treatment can reduce lesion size and behavioral deficits after moderate-to-severe bilateral injury to the medial...
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SubjectTerms Animal behavior
Animals
Attention
Behavior, Animal - drug effects
Biology and Life Sciences
Body weight
Brain
Brain injuries
Brain Injuries - drug therapy
Brain injury
Care and treatment
Cortex (frontal)
Development and progression
Disease Models, Animal
Dose-Response Relationship, Drug
Emergency medical care
Female
Females
Fuel consumption
Gender
Gender aspects
Gender differences
Head injuries
Injury prevention
Lesions
Male
Maze Learning - drug effects
Medicine and Health Sciences
Neuroprotective Agents - therapeutic use
Prefrontal cortex
Prefrontal Cortex - drug effects
Prefrontal Cortex - injuries
Prefrontal Cortex - pathology
Progesterone
Progesterone - therapeutic use
Progestins - therapeutic use
Rats
Rats, Sprague-Dawley
Research and Analysis Methods
Risk factors
Rodents
Sex differences
Sex Factors
Traumatic brain injury
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Title Progesterone Treatment Shows Benefit in Female Rats in a Pediatric Model of Controlled Cortical Impact Injury
URI https://www.ncbi.nlm.nih.gov/pubmed/26799561
https://www.proquest.com/docview/1759161445
https://www.proquest.com/docview/1760915675
https://pubmed.ncbi.nlm.nih.gov/PMC4723082
https://doaj.org/article/798670f97d6e404b9193c6237b5eb91e
http://dx.doi.org/10.1371/journal.pone.0146419
Volume 11
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