Physiologic progesterone reduces mitochondrial dysfunction and hippocampal cell loss after traumatic brain injury in female rats
Abstract
Growing literature suggests important sex-based differences in outcome following traumatic brain injury (TBI) in animals and humans. Progesterone has emerged as a key hormone involved in many potential neuroprotective pathways after acute brain injury and may be responsible for some of these differences. Many studies have utilized supraphysiologic levels of post-traumatic progesterone to reverse pathologic processes after TBI, but few studies have focused on the role of endogenous physiologic levels of progesterone in neuroprotection. We hypothesized that progesterone at physiologic serum levels would be neuroprotective in female rats after TBI and that progesterone would reverse early mitochondrial dysfunction seen in this model. Female, Sprague-Dawley rats were ovariectomized and implanted with silastic capsules containing either low or high physiologic range progesterone at 7 days prior to TBI. Control rats received ovariectomy with implants containing no hormone. Rats underwent controlled cortical impact to the left parietotemporal cortex and were evaluated for evidence of early mitochondrial dysfunction (1 h) and delayed hippocampal neuronal injury and cortical tissue loss (7 days) after injury. Progesterone in the low physiologic range reversed the early postinjury alterations seen in mitochondrial respiration and reduced hippocampal neuronal loss in both the CA1 and CA3 subfields. Progesterone in the high physiologic range had a more limited pattern of hippocampal neuronal preservation in the CA3 region only. Neither progesterone dose significantly reduced cortical tissue loss. These findings have implications in understanding the sex-based differences in outcome following acute brain injury.
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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 [143]
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- Authors
- Robertson, C. L., Puskar, A., Hoffman, G. E., Murphy, A. Z., Saraswati, M., & Fiskum, G.
- Affiliations
- University of Maryland, Baltimore (US)
- Corresponding author
- Robertson, Courtney L.
- Venue
- Experimental Neurology
- Publisher
- Elsevier BV
- Published
- 2006-01
- Volume
- 197
- Issue
- 1
- Pages
- 235-243
- ISSN
- 0014-4886 (ISSN-L)
- OpenAlex
- W2044821990
- Cited by
- 152
- References
- 55
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 6 · 2023: 3 · 2022: 2 · 2021: 5 · 2020: 3 · 2019: 8 · 2018: 7 · 2017: 9 · 2016: 10 · 2015: 10 · 2014: 12 · 2013: 15 · 2012: 5
- FWCI
- 4.53
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (K08 NS42805)
- U.S. Army Medical Command (DAMD 17-99-1-9483)
- Topics
- Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Automotive and Human Injury Biomechanics
- Keywords
- progesterone, traumatic brain injury, mitochondrial dysfunction, hippocampal neuronal loss, sex differences, neuroprotection, endogenous hormone levels, mitochondrial respiration, ovariectomy, controlled cortical impact, female rats
- MeSH terms
- Animals, Brain Injuries, Cell Count, Cerebral Cortex, Drug Implants, Female, Hippocampus, Mitochondria, Ovariectomy, Oxygen Consumption, Progesterone, Rats, Sprague-Dawley, Rats
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