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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 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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Morawska, M. M., Büchele, F., Moreira, C. G., Imbach, L., Noaín, D., & Baumann, C. R. (2016) · Journal of Neuroscience · doi:10.1523/jneurosci.3274-15.2016 · Cited by 49
Hazra, A., Macolino, C., Elliott, M. B., & Chin, J. (2014) · Journal of Neuroscience Research · doi:10.1002/jnr.23430 · Cited by 48
Sandsmark, D. K., Kumar, M. A., Woodward, C. S., Schmitt, S. E., Park, S., & Lim, M. M. (2016) · Journal of Head Trauma Rehabilitation · doi:10.1097/htr.0000000000000217 · Cited by 48
Self-citationSabir, M., Gaudreault, P.-O., Freyburger, M., Massart, R., Blanchet-Cohen, A., Jaber, M., Gosselin, N., & Mongrain, V. (2015) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2014.12.023 · Cited by 47
Flagged first, then by citations
1 of the 245 references couldn’t be matched to a known paper.
Research works printed but not linked: 3
- 2016, Sleep Disorders Associated With Traumatic Brain Injury, Pediatr Neurol, 60, 1
- 2015, Glutamatergic input to orexin neurons is decreased after mild traumatic brain injury and restored by dietary therapy, SLEEP (abstact), 55
- 1995, [EEG changes during sedation with gamma-hydroxybutyric acid], Anaesthesist, 44, 345
Cited by
Sorted by citations
Understanding and approaching excessive daytime sleepiness
Pérez‐Carbonell, L., Mignot, E. J.-M., Leschziner, G. D., & Dauvilliers, Y. A. (2022) · The Lancet · doi:10.1016/s0140-6736(22)01018-2 · Cited by 246
Sleep in the United States Military
Good, C. H., Brager, A. J., Capaldi, V. F., & Mysliwiec, V. (2019) · Neuropsychopharmacology · doi:10.1038/s41386-019-0431-7 · Cited by 204
Concussion Guidelines Step 2: Evidence for Subtype Classification
Lumba‐Brown, A., Teramoto, M., Bloom, O. J., Brody, D. L., Chesnutt, J. C., Clugston, J. R., Collins, M. W., Gioia, G. A., Kontos, A. P., Lal, A., et al. (2019) · Neurosurgery · doi:10.1093/neuros/nyz332 · Cited by 166
Concussion As a Multi-Scale Complex System: An Interdisciplinary Synthesis of Current Knowledge
Kenzie, E. S., Parks, E. L., Bigler, E. D., Lim, M. M., Chesnutt, J. C., & Wakeland, W. W. (2017) · Frontiers in Neurology · doi:10.3389/fneur.2017.00513 · Cited by 164
Self-citationComplement factor C1q mediates sleep spindle loss and epileptic spikes after mild brain injury
Holden, S. S., Grandi, F. C., Aboubakr, O., Higashikubo, B., Cho, F. S., Chang, A. H., Forero, A. O., Morningstar, A. R., Mathur, V., Kuhn, L. J., et al. (2021) · Science · doi:10.1126/science.abj2685 · Cited by 133
Metadata
- 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 › Clinical Neurology › Traumatic Brain Injury Research
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and related disorders
- Health Sciences › Medicine › Clinical 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.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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