Hypocretin-1 (orexin A) deficiency in acute traumatic brain injury
Open accessAbstract
Hypocretin-1 is involved in the regulation of the sleep-wake cycle. The authors prospectively assessed CSF hypocretin-1 levels in 44 consecutive patients with acute traumatic brain injury (TBI). Compared with controls, hypocretin-1 levels were abnormally lower in 95% of patients with moderate to severe TBI and in 97% of patients with posttraumatic brain CT changes. Hypocretin-1 deficiency after TBI may reflect hypothalamic damage and be linked with the frequent development of posttraumatic sleep-wake disorders.
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In Baumann et al. 2005, 30/31 severe TBI patients and 7/8 moderate TBI patients had low levels of orexin.
“Of the patients, 30/31 severe TBI patients and 7/8 patients with moderate TBI had low levels of orexin.”
From Effects of Traumatic Brain Injury on the Orexin/Hypocretin System (2025) · cites this paper as [56]
In Baumann et al. 2005, 37/44 TBI patients had low orexin levels.
“In this group of patients, 37/44, or 84%, had low orexin levels.”
From Effects of Traumatic Brain Injury on the Orexin/Hypocretin System (2025) · cites this paper as [56]
Patients with mild TBI still experience sleep disorders and show decreased orexin in the CSF.
“Patients with mild TBI still experience sleep disorders,59,60 and show decreased orexin in the CSF,56,57”
From Effects of Traumatic Brain Injury on the Orexin/Hypocretin System (2025) · cites this paper as [56]
Injury to ascending arousal pathways from the brainstem may contribute to chronic sleepiness after head trauma.
“Injury to ascending arousal pathways from the brainstem may contribute, but recent findings suggest a key role for the neuropeptides hypocretin-1 and -2 (also known as orexin-A and -B).2,4,5”
From Loss of hypocretin (orexin) neurons with traumatic brain injury (2009) · cites this paper as [4]
TBI patients have a marked reduction in CSF hypocretin-1 levels in the first days after injury.
“We recently found that TBI patients have a marked reduction in CSF hypocretin-1 levels in the first days after injury.4”
From Loss of hypocretin (orexin) neurons with traumatic brain injury (2009) · cites this paper as [4]
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Hypocretin (orexin) deficiency in human narcolepsy
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Self-citationThe diagnosis of head injury requires a classification based on computed axial tomography.
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Fos Expression in Orexin Neurons Varies with Behavioral State
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CSF hypocretin/orexin levels in narcolepsy and other neurological conditions
Ripley, B., Overeem, S., Fujiki, N., Nevsimalova, S., Uchino, M., Yesavage, J., Di Monte, D., Dohi, K., Melberg, A., Lammers, G. J., et al. (2001) · Neurology · doi:10.1212/wnl.57.12.2253 · Cited by 415 · see citing works
Self-citationDauvilliers, Y. A. (2003) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.74.12.1667 · Cited by 313 · see citing works
Multiple Forms of “Kiss-and-Run” Exocytosis Revealed by Evanescent Wave Microscopy
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Acute hypothalamic instability in traumatic brain injury: A case report
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Sleep-wake disturbances 6 months after traumatic brain injury: a prospective study
Baumann, C. R., Werth, E., Stocker, R., Ludwig, S., & Bassetti, C. L. (2007) · Brain · doi:10.1093/brain/awm109 · Cited by 380 · see citing works
Self-citationLoss of hypocretin (orexin) neurons with traumatic brain injury
Baumann, C. R., Bassetti, C. L., Valko, P. O., Haybaeck, J., Keller, M., Clark, E., Stocker, R., Tolnay, M., & Scammell, T. E. (2009) · Annals of Neurology · doi:10.1002/ana.21836 · Cited by 185 · see citing works
“Injury to ascending arousal pathways from the brainstem may contribute, but recent findings suggest a key role for the neuropeptides hypocretin-1 and -2 (also known as orexin-A and -B).(2,4,5) Hypocretins are made by a small cluster of neurons in the lateral hypothalamus that play an essential role in promoting wakefu…”
BackgroundSelf-citationSaber, M., Giordano, K. R., Hur, Y., Ortiz, J. B., Morrison, H., Godbout, J. P., Murphy, S. M., Lifshitz, J., & Rowe, R. K. (2020) · European Journal of Neuroscience · doi:10.1111/ejn.14611 · Cited by 46 · see citing works
Kousi, C., Lampri, E., Voulgaris, S., Vougiouklakis, T., Galani, V., & Mitselou, A. (2021) · Forensic Science International · doi:10.1016/j.forsciint.2021.110961 · Cited by 10 · see citing works
Effects of Traumatic Brain Injury on the Orexin/Hypocretin System
Somach, R. T., Lim, M. M., & Cohen, A. S. (2025) · Neurotrauma Reports · doi:10.1089/neur.2024.0111 · Cited by 2 · see citing works
- Authors
- Baumann, C. R., Stocker, R., Imhof, H. G., Trentz, O., Hersberger, M., Mignot, E., & Bassetti, C. L.
- Affiliations
- University Hospital Zurich (CH)
- Venue
- Neurology
- Published
- 2005-07-12
- Volume
- 65
- Issue
- 1
- Pages
- 147-149
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- OpenAlex
- W2044987694
- Cited by
- 191
- References
- 8
- Citations by year
- 2026: 6 · 2025: 12 · 2024: 3 · 2023: 2 · 2022: 8 · 2021: 10 · 2020: 9 · 2019: 13 · 2018: 12 · 2017: 10 · 2016: 11 · 2015: 13 · 2014: 9 · 2013: 17 · 2012: 11
- FWCI
- 3.42
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Locations
- Neurology (publishedVersion)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
- Keywords
- orexin-A, traumatic brain injury, cerebrospinal fluid, sleep-wake cycle, hypothalamic injury, moderate to severe brain injury
- MeSH terms
- Orexins, Adolescent, Adult, Aged, Autonomic Nervous System, Body Temperature, Brain Injuries, Female, Humans, Hypothalamic Area, Lateral, Hypothalamic Diseases, Hypothalamus, Hypothalamus, Posterior, Male, Middle Aged, Neural Pathways, Neuropeptides, Prospective Studies, Sleep, Sleep Wake Disorders, Wakefulness, Intracellular Signaling Peptides and Proteins
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