Acute peripheral inflammation and post‐traumatic sleep differ between sexes after experimental diffuse brain injury
Open accessAbstract
Identifying differential responses between sexes following traumatic brain injury (TBI) can elucidate the mechanisms behind disease pathology. Peripheral and central inflammation in the pathophysiology of TBI can increase sleep in male rodents, but this remains untested in females. We hypothesized that diffuse TBI would increase inflammation and sleep in males more so than in females. Diffuse TBI was induced in C57BL/6J mice and serial blood samples were collected (baseline, 1, 5, 7 days post‐injury [DPI]) to quantify peripheral immune cell populations and sleep regulatory cytokines. Brains and spleens were harvested at 7DPI to quantify central and peripheral immune cells, respectively. Mixed‐effects regression models were used for data analysis. Female TBI mice had 77%–124% higher IL‐6 levels than male TBI mice at 1 and 5DPI, whereas IL‐1β and TNF‐α levels were similar between sexes at all timepoints. Despite baseline sex differences in blood‐measured Ly6C high monocytes (females had 40% more than males), TBI reduced monocytes by 67% in TBI mice at 1DPI. Male TBI mice had 31%–33% more blood‐measured and 31% more spleen‐measured Ly6G + neutrophils than female TBI mice at 1 and 5DPI, and 7DPI, respectively. Compared with sham, TBI increased sleep in both sexes during the first light and dark cycles. Male TBI mice slept 11%–17% more than female TBI mice, depending on the cycle. Thus, sex and TBI interactions may alter the peripheral inflammation profile and sleep patterns, which might explain discrepancies in disease progression based on sex.
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One study found no differences by sex with regard to orexin neurons themselves but did find differences in sleep parameters after injury.
“One study found no differences by sex with regard to orexin neurons themselves but did find differences in sleep parameters after injury.71”
From Effects of Traumatic Brain Injury on the Orexin/Hypocretin System (2025) · cites this paper as [71]
The Results section reports that female TBI mice had 16% more orexin-positive neurons than male TBI mice, contrary to the claim of no sex difference in those neurons. The Discussion does support the other part of the sentence: post-traumatic sleep percentage differed between male and female TBI mice during the first dark and second light cycles. (LLM, conf=0.88)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredSome animal studies report a disordered sleep phenotype of increased wakefulness, more latency to sleep, or insomnia, which are also phenotypes of sleep disorders in human TBI patients.
“Some studies report a disordered sleep phenotype of increased wakefulness, more latency to sleep, or insomnia in animals,65,70–72 which are also phenotypes of sleep disorders in human TBI patients.”
From Effects of Traumatic Brain Injury on the Orexin/Hypocretin System (2025) · cites this paper as [71]
The Results report that female TBI mice slept 17% less than sham mice during the second light cycle, consistent with increased wakefulness in that group and period. The Discussion notes sleep disruption in human TBI patients, but the paper does not establish increased sleep latency or insomnia in its mice, or specifically identify those phenotypes in human TBI patients. Pages were not provided in our copy. (LLM, conf=0.83)
Experimental — accuracy not yet measuredSome studies show no significant differences in orexin neurons between injured and sham-injured animals.
“Some studies show no significant differences in orexin neurons between injured and sham-injured animals.44,67,69,71,74”
From Effects of Traumatic Brain Injury on the Orexin/Hypocretin System (2025) · cites this paper as [71]
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Acute Post-Traumatic Sleep May Define Vulnerability to a Second Traumatic Brain Injury in Mice
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Midline (central) fluid percussion model of traumatic brain injury in pediatric and adolescent rats.
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Self-citation
- Authors
- Saber, M., Giordano, K. R., Hur, Y., Ortiz, J. B., Morrison, H., Godbout, J. P., Murphy, S. M., Lifshitz, J., & Rowe, R. K.
- Affiliations
- Barrow Neurological Institute (US)
- University of Arizona (US)
- The Ohio State University (US)
- University of Arizona College of Medicine- Phoenix (US)
- Corresponding author
- Rowe, Rachel K.
- ORCID
- Venue
- European Journal of Neuroscience
- Publisher
- Wiley
- Published
- 2019-11-27
- Volume
- 52
- Issue
- 1
- Pages
- 2791-2814
- ISSN
- 0953-816X (ISSN-L)
- 1460-9568
- PMC
- PMC7195243
- OpenAlex
- W2986402309
- Cited by
- 46
- References
- 112
- Citations by year
- 2026: 9 · 2025: 7 · 2024: 6 · 2023: 6 · 2022: 7 · 2021: 3 · 2020: 8
- FWCI
- 3.04
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- European Journal of Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Foundation for the National Institutes of Health (T32 AG044402)
- Topics
- Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- traumatic brain injury, sex differences, sleep, peripheral inflammation, interleukin-6, monocytes, neutrophils, spleen, cytokines, diffuse brain injury, C57BL/6J mice
- MeSH terms
- Brain Injuries, Diffuse, Brain Injuries, Traumatic, Animals, Disease Models, Animal, Female, Inflammation, Male, Mice, Inbred C57BL, Sleep, Mice
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