Sleep-Wake Disturbances After Traumatic Brain Injury: Synthesis of Human and Animal Studies
Open accessAbstract
Sleep-wake disturbances following traumatic brain injury (TBI) are increasingly recognized as a serious consequence following injury and as a barrier to recovery. Injury-induced sleep-wake disturbances can persist for years, often impairing quality of life. Recently, there has been a nearly exponential increase in the number of primary research articles published on the pathophysiology and mechanisms underlying sleep-wake disturbances after TBI, both in animal models and in humans, including in the pediatric population. In this review, we summarize over 200 articles on the topic, most of which were identified objectively using reproducible online search terms in PubMed. Although these studies differ in terms of methodology and detailed outcomes; overall, recent research describes a common phenotype of excessive daytime sleepiness, nighttime sleep fragmentation, insomnia, and electroencephalography spectral changes after TBI. Given the heterogeneity of the human disease phenotype, rigorous translation of animal models to the human condition is critical to our understanding of the mechanisms and of the temporal course of sleep-wake disturbances after injury. Arguably, this is most effectively accomplished when animal and human studies are performed by the same or collaborating research programs. Given the number of symptoms associated with TBI that are intimately related to, or directly stem from sleep dysfunction, sleep-wake disorders represent an important area in which mechanistic-based therapies may substantially impact recovery after TBI.
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Animal models recapitulate sleep phenotypes of disordered sleep in humans, especially excessive daytime sleepiness.
“Animal models recapitulate sleep phenotypes of disordered sleep in humans, especially that of EDS.22,44,45,48,49,64–73”
From Effects of Traumatic Brain Injury on the Orexin/Hypocretin System (2025) · cites this paper as [22]
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Sleep Supports Memory and Learning: Implications for Clinical Practice in Speech-Language Pathology
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Reddy, D. S., Golub, V. M., Ramakrishnan, S., Churn, S. B., Shapiro, L. A., Iannucci, J., Pitkänen, A., Galanopoulou, A. S., Maganti, R. K., & Boison, D. (2025) · Pharmacological Reviews · doi:10.1016/j.pharmr.2025.100080 · Cited by 18 · see citing works
McKeon, A. B., Stocker, R., & Germain, A. (2019) · Neurorehabilitation · doi:10.3233/nre-192804 · Cited by 16 · see citing works
Kinney, A. R., Yan, X.-D., Schneider, A. L., King, S., Forster, J. E., Bahraini, N. H., & Brenner, L. A. (2022) · Frontiers in Rehabilitation Sciences · doi:10.3389/fresc.2022.964420 · Cited by 16 · see citing works
Intracerebral hemorrhage in the mouse altered sleep-wake patterns and activated microglia
Giordano, K. R., Denman, C. R., Dollish, H. K., Fernandez, F., Lifshitz, J., Akhter, M., & Rowe, R. K. (2020) · Experimental Neurology · doi:10.1016/j.expneurol.2020.113242 · Cited by 16 · see citing works
Treatments for sleep disturbances in individuals with acquired brain injury: A systematic review
Pilon, L., Frankenmolen, N., & Bertens, D. (2021) · Clinical Rehabilitation · doi:10.1177/02692155211014827 · Cited by 11 · see citing works
Bell, K. R., Fogelberg, D. J., Barber, J. K., Nakase‐Richardson, R., Zumsteg, J. M., Dubiel, R., Dams-O’Connor, K., & Hoffman, J. M. (2021) · Brain Injury · doi:10.1080/02699052.2021.1871952 · Cited by 15 · see citing works
Morrow, E. L., Mayberry, L. S., & Duff, M. C. (2023) · Neuropsychologia · doi:10.1016/j.neuropsychologia.2023.108518 · Cited by 15 · see citing works
Borniger, J. C., Ungerleider, K., Zhang, N., Karelina, K., Magalang, U. J., & Weil, Z. M. (2018) · Neuroscience · doi:10.1016/j.neuroscience.2018.01.064 · Cited by 15 · see citing works
Sleep and agitation during subacute traumatic brain injury rehabilitation: A scoping review
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Govindarajulu, M., Patel, M. Y., Wilder, D. M., Long, J. B., & Arun, P. (2022) · Brain Sciences · doi:10.3390/brainsci12101340 · Cited by 15 · see citing works
McGowan, J. C., Ladner, L. R., Shubeck, C. X., Tapia, J., LaGamma, C. T., Anqueira-González, A., DeFrancesco, A., Chen, B. K., Hunsberger, H. C., Sydnor, E., et al. (2023) · Biological Psychiatry · doi:10.1016/j.biopsych.2023.06.030 · Cited by 14 · see citing works
Microglia depletion and cognitive functions after brain injury: From trauma to galactic cosmic ray
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Lipoxins as Modulators of Diseases
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Mild Traumatic Brain Injury Affects Orexin/Hypocretin Physiology Differently in Male and Female Mice
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Self-citationSleep disturbance and cognition in people with TBI
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Perceiving traumatic brain injury from glymphatic system
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Effect of Sleep-Related Symptoms on Recovery From a Sport-Related Concussion
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Morrow, E. L., Mattis-Roesch, H., Walsh, K., & Duff, M. C. (2023) · Journal of Head Trauma Rehabilitation · doi:10.1097/htr.0000000000000894 · Cited by 11 · see citing works
Vishwanath, M., Jafarlou, S., Shin, I., Dutt, N. D., Rahmani, A. M., Jones, C. E., Lim, M. M., & Cao, H. (2021) · Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) · doi:10.1109/embc46164.2021.9630423 · Cited by 11 · see citing works
Self-citationSleep disorders in traumatic brain injury
Paredes, I., Navarro-Main, B., & Lagares, A. (2020) · Neurocirugía (English Edition) · doi:10.1016/j.neucie.2020.12.001 · Cited by 11 · see citing works
- Authors
- Sandsmark, D. K., Elliott, J. E., & Lim, M. M.
- Affiliations
- University of Pennsylvania (US)
- Oregon Health & Science University (US)
- Venue
- Sleep
- Publisher
- Oxford University Press (OUP)
- Published
- 2017-03-17
- Volume
- 40
- Issue
- 5
- ISSN
- 0161-8105 (ISSN-L)
- 1550-9109
- PMC
- PMC6251652
- OpenAlex
- W2596622414
- Cited by
- 183
- References
- 245
- Citations by year
- 2026: 5 · 2025: 19 · 2024: 14 · 2023: 19 · 2022: 31 · 2021: 29 · 2020: 25 · 2019: 19 · 2018: 20 · 2017: 2
- FWCI
- 2.39
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- public-domain
- Locations
- SLEEP (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, public-domain)
- PubMed Central (publishedVersion, public-domain)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Veterans Affairs (IK2 BX002712)
- National Center for Complementary and Integrative Health (T32AT002688)
- Topics
- Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and related disorders
- Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Keywords
- traumatic brain injury, sleep-wake disturbances, excessive daytime sleepiness, sleep fragmentation, insomnia, pediatric traumatic brain injury, sleep disorders, brain injury recovery
- MeSH terms
- Brain Injuries, Traumatic, Animals, Disease Models, Animal, Electroencephalography, Humans, Sleep Initiation and Maintenance Disorders, Phenotype, Sleep Wake Disorders
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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