Progesterone protects mitochondrial function in a rat model of pediatric traumatic brain injury
Abstract
Progesterone has been studied extensively in preclinical models of adult traumatic brain injury (TBI), and has advanced to clinical trials in adults with TBI. However, there are very few preclinical studies in pediatric TBI models investigating progesterone for neuroprotection. Immature male and female rats (postnatal day, PND 17-21) underwent controlled cortical impact (CCI) to the left parietal cortex. Rats received either progesterone (10 mg/kg) at 1 h (i.p.) and 6 h (s.c.) after TBI or vehicle (22.5 % cyclohexdrin), and were compared to naïve, age-matched littermates. At 24 h after CCI, brain mitochondria were isolated from the ipsilateral hemisphere. Active (State 3) and resting (State 4) mitochondrial respiration were measured, and mitochondrial respiratory control ratio (RCR, State 3/State 4) was determined. Total mitochonidral glutathione content was measured. A separate group of rats were studied for histology, and received progesterone or vehicle every 24 h (s.c.) for 7 days. In male rats, TBI reduced mitochondrial RCR, and progesterone preserved mitochondrial RCR. This improvement of RCR was predominantly through significant decreases in State 4 respiratory rates. In female rats, post-injury treatment with progesterone did not significantly improve mitochondrial RCR. Normal (uninjured) male rats had lower mitochondrial glutathione content than normal female rats. After TBI, progesterone prevented loss of mitochondrial glutathione in male rats only. Tissue loss was reduced in progesterone treated female rats at 7d after CCI. Future studies will be directed at correlation with neurologic outcome testing. These preclinical studies could provide information for planning future clinical trials of progesterone treatment in children with TBI.
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Sex may influence the response to exogenous hormone treatments as seen in a rat model of pediatric TBI, where progesterone improved mitochondrial respiratory control ratio and glutathione levels in males but reduced lesion volumes in females.
“Sex may also influence the response to exogenous hormone treatments as seen in a rat model of pediatric TBI, where progesterone improved mitochondrial respiratory control ratio and glutathione levels in males but reduced lesion volumes in females. 65”
From Sex Differences in Traumatic Brain Injury: What We Know and What We Should Know (2019) · cites this paper as [65]
Progesterone treatment prevented loss of the antioxidant glutathione in juvenile male rats, but not in females.
“prevented loss of the antioxidant glutathione in juvenile male rats, but not in females.”
From Sex Differences in Traumatic Brain Injury: What We Know and What We Should Know (2019) · cites this paper as [65]
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Sex Differences in Traumatic Brain Injury: What We Know and What We Should Know
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- Authors
- Robertson, C. L., & Saraswati, M.
- Affiliations
- Johns Hopkins University (US)
- Corresponding author
- Robertson, Courtney L.
- Venue
- Journal of Bioenergetics and Biomembranes
- Published
- 2014-10-28
- Volume
- 47
- Issue
- 1-2
- Pages
- 43-51
- ISSN
- 0145-479X (ISSN-L)
- 1573-6881
- OpenAlex
- W2021063378
- Cited by
- 56
- References
- 65
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 2 · 2023: 1 · 2022: 4 · 2021: 5 · 2020: 5 · 2019: 11 · 2018: 7 · 2017: 7 · 2016: 5 · 2015: 3
- FWCI
- 3.26
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Journal of Bioenergetics and Biomembranes (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Johns Hopkins University
- Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Medicine
- Topics
- Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- progesterone, pediatric traumatic brain injury, neuroprotection, mitochondrial function, mitochondrial respiration, respiratory control ratio, mitochondrial glutathione, sex differences, controlled cortical impact, immature rats, tissue loss
- MeSH terms
- Animals, Brain Injuries, Cerebral Cortex, Child, Child, Preschool, Disease Models, Animal, Female, Glutathione, Humans, Male, Mitochondria, Oxygen Consumption, Progestins, Progesterone, Sex Characteristics, Rats, Sprague-Dawley, Rats
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