Damage to histaminergic tuberomammillary neurons and other hypothalamic neurons with traumatic brain injury
Open accessAbstract
The need for increased sleep after traumatic brain injury is a common and disabling complaint, yet its etiology is unknown. Previous studies have demonstrated diffuse damage to various hypothalamic systems, but the integrity of the histaminergic tuberomammillary nucleus, a major arousal‐promoting system located in the posterior hypothalamus, has never been examined in head trauma patients. Here, we demonstrate that severe head trauma is associated with a marked loss (41%) of histaminergic neurons. Reduced histamine signaling may contribute to increased sleep need, and therapies that enhance histaminergic tone may improve arousal after head trauma or other conditions. ANN NEUROL 2015;77:177–182
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In Valko et al. 2015, 12 TBI patients experienced a 21% loss of orexin neurons compared to controls.
“In Valko et al. 2015, 12 TBI patients experienced a 21% loss of orexin neurons compared to controls.46”
From Effects of Traumatic Brain Injury on the Orexin/Hypocretin System (2025) · cites this paper as [46]
Some studies have evidence of reduced numbers of MCH neurons after injury, observed after severe TBI.
“some studies have evidence of reduced numbers of MCH neurons after injury. However, this outcome was observed after severe TBI,46,47”
From Effects of Traumatic Brain Injury on the Orexin/Hypocretin System (2025) · cites this paper as [46]
In the same prior series, there was a 21% loss of hypocretin neurons.
“In a series of 12 patients with severe TBI and 16 matched controls, we found a 41% loss of histaminergic TMN neurons and a 21% loss of hypocretin neurons.5”
From Damage to Arousal-Promoting Brainstem Neurons with Traumatic Brain Injury (2016) · cites this paper as [5]
In a prior series of 12 patients with severe TBI and 16 matched controls, there was a 41% loss of histaminergic TMN neurons.
“In a series of 12 patients with severe TBI and 16 matched controls, we found a 41% loss of histaminergic TMN neurons and a 21% loss of hypocretin neurons.5”
From Damage to Arousal-Promoting Brainstem Neurons with Traumatic Brain Injury (2016) · cites this paper as [5]
Cites
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 · cited 1× · see citing works
“Surprisingly little is known about injury to the hypothalamus and other wake-promoting brain regions in TBI, but in a pilot study of 4 TBI patients and 4 controls without head injury, we found a 27% loss of wake-promoting orexin (hypocretin) neurons.(7) To improve our understanding of injury to wake-promoting circuitr…”
BackgroundSelf-citationModafinil ameliorates excessive daytime sleepiness after traumatic brain injury
Kaiser, P. R., Valko, P. O., Werth, E., Thomann, J., Meier, J., Stocker, R., Bassetti, C. L., & Baumann, C. R. (2010) · Neurology · doi:10.1212/wnl.0b013e3181fd62a2 · Cited by 150 · see citing works
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Sleep-Wake Disturbances After Traumatic Brain Injury: Synthesis of Human and Animal Studies
Sandsmark, D. K., Elliott, J. E., & Lim, M. M. (2017) · Sleep · doi:10.1093/sleep/zsx044 · Cited by 183 · see citing works
Damage to Arousal-Promoting Brainstem Neurons with Traumatic Brain Injury
Valko, P. O., Gavrilov, Y. V., Yamamoto, M., Noaín, D., Reddy, H., Haybaeck, J., Weis, S., Baumann, C. R., & Scammell, T. E. (2016) · Sleep · doi:10.5665/sleep.5844 · Cited by 49 · see citing works
Self-citationKousi, 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
- Valko, P. O., Gavrilov, Y. V., Yamamoto, M., Finn, K., Reddy, H., Haybaeck, J., Weis, S., Scammell, T. E., & Baumann, C. R.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- Medical University of Graz (AT)
- Johannes Kepler University of Linz (AT)
- Corresponding author
- Valko, Philipp O.
- ORCID
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 2014-11-20
- Volume
- 77
- Issue
- 1
- Pages
- 177-182
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- OpenAlex
- W1577135445
- Cited by
- 78
- References
- 3
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 3 · 2023: 7 · 2022: 3 · 2021: 6 · 2020: 6 · 2019: 7 · 2018: 13 · 2017: 4 · 2016: 14 · 2015: 7 · 2013: 1
- FWCI
- 5.44
- Type
- journal article
- Language
- en
- Open access
- green
- www.zora.uzh.ch
- Licence
- Locations
- Annals of Neurology (publishedVersion)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- Swiss National Science Foundation (no. 32003B-125504)
- Topics
- Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Keywords
- traumatic brain injury, histaminergic neurons, tuberomammillary nucleus, hypothalamic neurons, histamine signaling, arousal, posterior hypothalamus, neuronal loss
- MeSH terms
- Orexins, Aged, Aged, 80 and over, Austria, Brain Injuries, Female, Glial Fibrillary Acidic Protein, Histamine, Histidine Decarboxylase, Humans, Hypothalamic Area, Lateral, Hypothalamic Hormones, Hypothalamus, Male, Melanins, Neurons, Neuropeptides, Pituitary Hormones, Trauma Severity Indices, Intracellular Signaling Peptides and Proteins
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