The DOI matches its Crossref record; 25 of the 25 references it cites were found in a registry or an index; 16 of the 32 sources its claims cite were checked for support.
Loss of hypocretin (orexin) neurons with traumatic brain injury
Open accessAbstract
Chronic, daytime sleepiness is a major, disabling symptom for many patients with traumatic brain injury (TBI), but thus far, its etiology is not well understood. Extensive loss of the hypothalamic neurons that produce the wake‐promoting neuropeptide hypocretin (orexin) causes the severe sleepiness of narcolepsy, and partial loss of these cells may contribute to the sleepiness of Parkinson disease and other disorders. We have found that the number of hypocretin neurons is significantly reduced in patients with severe TBI. This observation highlights the often overlooked hypothalamic injury in TBI and provides new insights into the causes of chronic sleepiness in patients with TBI. Ann Neurol 2009;66:555–559
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Written from the paper’s full text.
TL;DR
In postmortem hypothalami from 4 patients with severe TBI versus 4 controls, hypocretin neuron number was significantly reduced by 27%. This suggests that hypothalamic hypocretin neuron loss may contribute to chronic sleepiness after TBI.
Key findings
- TBI subjects had 27% fewer hypocretin neurons than controls (23,655 ± 5,035 vs. 32,318 ± 3,060 neurons, p = 0.001).
- MCH neurons were 31% fewer in TBI subjects (39,540 ± 10,900 vs. 57,176 ± 24,016), but this was not quite statistically significant (p = 0.06); excluding one female control with low MCH neuron numbers, TBI subjects had 29% fewer hypocretin neurons (p = 0.002) and 40% fewer MCH neurons (p = 0.003).
- GFAP-labeled astrocyte density was higher in TBI patients than controls (21 ± 12 vs. 7 ± 2 per mm², p < 0.001), and patients with more severe hypocretin neuron loss had more GFAP-labeled astrocytes (r = −0.46, p = 0.01).
- TBI hypothalami also showed intense perivascular hypocretin immunoreactivity, and many hypocretin neurons were small and pyknotic with reduced hypocretin fiber density.
Methods
- Autopsy brains from 4 patients who died 7 to 42 days (mean 19) after severe TBI and 4 control subjects with no clinical evidence of TBI or other neurological disorders; TBI patients were younger (51 ± 19 years) than controls (69 ± 18 years), and all subjects were male except one woman in the control group.
- Immunohistochemistry for hypocretin-1, MCH, and GFAP; hypocretin and MCH neurons were counted across a 1:24 series of the entire hypothalamus with Abercrombie correction, and GFAP-immunolabeled astrocytes were counted in 30 randomly selected 400 by 400 µm sites within the lateral and posterior hypothalamus.
- Cell counts were compared between groups using Student’s t-tests.
Limitations
- Stated by the paper: the study examined a small number of brains, control subjects were not fully matched, other wake-promoting systems were not examined, and the patients had fatal TBI, probably introducing selection bias; non-fatal TBI may be associated with less severe hypocretin neuron loss.
- Evident from the text: this is described as a pilot study with severe/fatal TBI cases, so findings may not generalize to milder or non-fatal TBI, and the autopsy design cannot directly establish that hypocretin loss causes chronic sleepiness.
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Claims the paper makes
11 Own result · 10 Own interpretation · 9 Partly supported · 9 Own method · 7 No full text of the sources · 2 Supported · 1 Sources not found · 1 No basis given · accuracy not yet measured
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“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”
§ Loss of hypocretin (orexin) neurons with traumatic brain injury > Introduction
What the sources say
- Partly supportedcites [2] Baumann CR Werth E Stocker R Sleep-wake disturbances 6 months after traumatic brain injury: a prospective study Brain 2007 130 1873 1883 17584779 sourceExperimental — accuracy not yet measured
The section on clinical characteristics and potential causes proposes that TBI may damage hypocretin neurons or their axons, contributing to post-traumatic sleepiness. It does not identify injury to ascending arousal pathways from the brainstem as that mechanism. The risk-factors section reports no association between lesion location and sleep-wake disturbances; outcomes in patients with visible brainstem or hypothalamic lesions did not differ from those of other patients. Page numbers were not available in our copy. (LLM, conf=0.84)
- Not checked — no full text of the sourcecites [4] Baumann CR Stocker R Imhof HG Hypocretin-1 (orexin A) deficiency in acute traumatic brain injury Neurology 2005 65 147 149 16009905 source
- Partly supportedcites [5] España RA Scammell TE Sleep neurobiology for the clinician Sleep 2004 27 811 820 15283019 sourceExperimental — accuracy not yet measured
The review’s Arousal Network section says lesions of the rostral reticular formation can disrupt wakefulness because they also damage arousal fibers. Its introductory discussion reports excessive sleepiness after injury to wake-promoting regions, but it does not establish that brainstem pathway injury contributes to chronic sleepiness specifically after head trauma. Page numbers are unavailable in our copy. (LLM, conf=0.84)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Even after 6 months recovery, many TBI patients with EDS have persistently low hypocretin-1 levels.2”
§ Loss of hypocretin (orexin) neurons with traumatic brain injury > Introduction
What the sources say
- Partly supportedcites [2] Baumann CR Werth E Stocker R Sleep-wake disturbances 6 months after traumatic brain injury: a prospective study Brain 2007 130 1873 1883 17584779 sourceExperimental — accuracy not yet measured
The Laboratory studies section reports that hypocretin-1 remained low in 4 of 21 patients at six months, while it was normal in 17. The Clinical characteristics section says levels were lower in patients with EDS, but does not establish that many patients with EDS had persistently low levels. The claim overstates the prevalence of persistent deficiency. (LLM, conf=0.88)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Selective loss of the hypocretin-producing neurons causes sleepiness and cataplexy in over 90% of patients with narcolepsy,5–9”
§ Loss of hypocretin (orexin) neurons with traumatic brain injury > Introduction
What the sources say
- Partly supportedcites [5] España RA Scammell TE Sleep neurobiology for the clinician Sleep 2004 27 811 820 15283019 sourceExperimental — accuracy not yet measured
The Orexin/Hypocretin section (page unavailable) links loss of orexin neurons to difficulty maintaining wakefulness and describes cataplexy with deficient orexin signaling. But its figure is about 90% of patients with narcolepsy *and cataplexy* having undetectable cerebrospinal-fluid orexin—not over 90% of all patients with narcolepsy having selective neuronal loss that causes both symptoms. (LLM, conf=0.88)
- Not checked — no full text of the sourcecites [6] Adamantidis AR Zhang F Aravanis AM Neural substrates of awakening probed with optogenetic control of hypocretin neurons Nature 2007 450 420 424 17943086 PMC6744371 source
- Not checked — no full text of the sourcecites [7] Peyron C Faraco J Rogers W A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains Nat Med 2000 6 991 997 10973318 source
- Not checked — no full text of the sourcecites [8] Thannickal TC Moore RY Nienhuis R Reduced number of hypocretin neurons in human narcolepsy Neuron 2000 27 469 474 11055430 PMC8760623 source
- Partly supportedcites [9] Crocker A España RA Papadopoulou M Concomitant loss of dynorphin, NARP, and orexin in narcolepsy Neurology 2005 65 1184 1188 16247044 PMC2254145 sourceExperimental — accuracy not yet measured
The Conclusions (page unavailable) say that narcolepsy with cataplexy is likely caused by loss of orexin-producing neurons, and the Discussion links disrupted orexin signaling to sleepiness and cataplexy. The paper does not establish that this occurs in over 90% of patients: its Results report roughly 90% or greater neuron loss in two people with narcolepsy and cataplexy, not a percentage of patients. (LLM, conf=0.87)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Coma and obtundation are common during the acute period, but even after 6 months recovery, 43% of patients have symptoms of sleep disorders.2,3”
§ Loss of hypocretin (orexin) neurons with traumatic brain injury > Introduction
What the sources say
- Partly supportedcites [2] Baumann CR Werth E Stocker R Sleep-wake disturbances 6 months after traumatic brain injury: a prospective study Brain 2007 130 1873 1883 17584779 sourceExperimental — accuracy not yet measured
The Fig. 3 caption (Single patient reports; page unavailable) reports that 28 of 65 patients (43%) had sleep–wake disturbances for which no cause other than traumatic brain injury was identified. But it reports sleep–wake disturbances in 47 of 65 patients overall, so 43% is the rate for a narrower group, not the overall rate implied by the claim. (LLM, conf=0.88)
- Partly supportedcites [3] Castriotta RJ Wilde MC Lai JM Prevalence and consequences of sleep disorders in traumatic brain injury J Clin Sleep Med 2007 3 349 356 17694722 PMC1978308 sourceExperimental — accuracy not yet measured
The Discussion reports that 47% of the TBI sample had a diagnosed sleep disorder, and Table 4 includes patients studied more than six months after injury. It does not report that 43% had symptoms after six months of recovery; the stated percentage, measure, and time-specific estimate are unsupported. (LLM, conf=0.84)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Double immunofluorescence staining showed that patients with more severe loss of hypocretin neurons had more GFAP-labeled astrocytes (r=−0.46, p=0.01).”
§ Loss of hypocretin (orexin) neurons with traumatic brain injury > Results
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Though TBI brains contained fewer hypocretin neurons, the neurons were distributed in a normal pattern, thus demonstrating the reliability and completeness of the cell counts (Figure 2).”
§ Loss of hypocretin (orexin) neurons with traumatic brain injury > Results
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The number of hypocretin neurons in TBI subjects was 27% less than in controls (23,655±5,035 vs. 32,318±3,060 neurons, p = 0.001) (Figure 1).”
- Also stated in: § Abstract · plain
“We have found that the number of hypocretin neurons is significantly reduced in patients with severe TBI.”
- Also stated in: § Discussion · plain
“In this pilot study, we found that patients with severe TBI have a significant loss of hypocretin-producing neurons.”
§ Loss of hypocretin (orexin) neurons with traumatic brain injury > Results
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Abstract · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The density of astrocytes as assessed by GFAP staining was significantly higher (21±12 vs. 7±2 per mm2, p<0.001) in TBI patients than in controls (Supplemental Figure B).”
§ Loss of hypocretin (orexin) neurons with traumatic brain injury > Results
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This amorphous staining was present around small vessels in the posterior and lateral hypothalamus but not elsewhere.”
§ Loss of hypocretin (orexin) neurons with traumatic brain injury > Results
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Hypothalami from TBI patients also contained intense perivascular hypocretin immunoreactivity (Figure 3).”
§ Loss of hypocretin (orexin) neurons with traumatic brain injury > Results
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Probably not a substantial claim. 17
- It may state two separate claims as one. 14
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“and identical symptoms occur in mice genetically lacking hypocretins.10”
§ Loss of hypocretin (orexin) neurons with traumatic brain injury > Introduction
What the sources say
- Partly supportedcites [10] Chemelli RM Willie JT Sinton CM Narcolepsy in orexin knockout mice: molecular genetics of sleep regulation Cell 1999 98 437 451 10481909 sourceExperimental — accuracy not yet measured
The Discussion reports that mice lacking orexin (hypocretin) have narcoleptic attacks and sleep dysregulation remarkably similar to human narcolepsy. It does not establish that the symptoms are identical: the authors say they cannot clearly distinguish the mice’s narcoleptic from cataplectic episodes and note an EEG feature not reported in humans or dogs. (LLM, conf=0.82)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Chronic, daytime sleepiness is a major, disabling symptom for many patients with traumatic brain injury (TBI), but thus far, its etiology is not well understood.”
- Also stated in: § Introduction · plain
“Though chronic sleepiness is common after head trauma, the cause remains unclear.”
§ Loss of hypocretin (orexin) neurons with traumatic brain injury > Abstract
What the sources say
- Supportedcites [2] Baumann CR Werth E Stocker R Sleep-wake disturbances 6 months after traumatic brain injury: a prospective study Brain 2007 130 1873 1883 17584779 source
The Clinical characteristics and potential causes section reports excessive daytime sleepiness in 38% of patients six months after TBI. The quality-of-life section says that sleep–wake complaints, particularly daytime sleepiness, significantly affect quality of life and social functioning; the Circadian sleep–wake disorders section says their neurobiological bases are unknown. Page numbers are unavailable in our copy. (LLM, conf=0.91)
- Partly supportedcites [3] Castriotta RJ Wilde MC Lai JM Prevalence and consequences of sleep disorders in traumatic brain injury J Clin Sleep Med 2007 3 349 356 17694722 PMC1978308 sourceExperimental — accuracy not yet measured
The Discussion reports a high prevalence of excessive daytime sleepiness after TBI and poorer cognitive and vigilance performance in sleepy subjects. It says functional disability is possible but that the impact on day-to-day functioning has not been established; it also cannot determine whether some sleep disorders preceded the injury. The paper therefore supports the prevalence and uncertainty about cause, but not the stronger claim that chronic sleepiness is an established major disabling symptom. (LLM, conf=0.85)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Also stated in: § Introduction · plain
Every source the paper cites for this claim was checked and supports it.
In the paper
“In a prospective study of 65 TBI patients, 1 in 4 patients reported excessive daytime sleepiness (EDS) irrespective of the location or severity of the head trauma.2”
§ Loss of hypocretin (orexin) neurons with traumatic brain injury > Introduction
What the sources say
- Supportedcites [2] Baumann CR Werth E Stocker R Sleep-wake disturbances 6 months after traumatic brain injury: a prospective study Brain 2007 130 1873 1883 17584779 source
The Abstract (page unavailable) reports 65 patients and subjective excessive daytime sleepiness in 18 (28%), consistent with roughly one in four patients reporting EDS. The Identification of risk factors section (page unavailable) reports no association between injury localization and post-traumatic sleep–wake disturbances, and says severe TBI was not associated with disturbances other than hypersomnia. (LLM, conf=0.90)
plainn = 65- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Another study of 87 patients revealed similar results, with sleepiness in 25% after TBI.3”
§ Loss of hypocretin (orexin) neurons with traumatic brain injury > Introduction
What the sources say
- Supportedcites [3] Castriotta RJ Wilde MC Lai JM Prevalence and consequences of sleep disorders in traumatic brain injury J Clin Sleep Med 2007 3 349 356 17694722 PMC1978308 source
The Results report 87 TBI subjects, and Table 1 lists 22 (25%) in the sleepy group, defined by an MSLT score below 10. The Discussion likewise reports excessive daytime sleepiness in approximately 26% of the sample. (LLM, conf=0.94)
plainn = 87- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Hypocretins are made by a small cluster of neurons in the lateral hypothalamus that play an essential role in promoting wakefulness.”
§ Loss of hypocretin (orexin) neurons with traumatic brain injury > Introduction
What the sources say
- Partly supportedcites [5] España RA Scammell TE Sleep neurobiology for the clinician Sleep 2004 27 811 820 15283019 sourceExperimental — accuracy not yet measured
The Orexin/Hypocretin section says hypocretins are produced by neurons in the lateral and posterior hypothalamus and that these neurons play an essential role in stabilizing wakefulness. It does not establish that they form a small cluster, and it names the posterior hypothalamus as well as the lateral hypothalamus. (LLM, conf=0.79)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“In controls, the total number of hypocretin neurons and their distribution across the lateral and posterior hypothalamus were similar to prior reports.7,8,14,15”
§ Loss of hypocretin (orexin) neurons with traumatic brain injury > Results
What the sources say
- Not checked — no full text of the sourcecites [7] Peyron C Faraco J Rogers W A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains Nat Med 2000 6 991 997 10973318 source
- Not checked — no full text of the sourcecites [8] Thannickal TC Moore RY Nienhuis R Reduced number of hypocretin neurons in human narcolepsy Neuron 2000 27 469 474 11055430 PMC8760623 source
- Partly supportedcites [14] Fronczek R Overeem S Lee SY Hypocretin (orexin) loss in Parkinson's disease Brain 2007 130 1577 1585 17470494 sourceExperimental — accuracy not yet measured
The Hypocretin-1 cell number section reports a control median of 36,842 neurons, and the Hypocretin-1 histochemistry section says their distribution matched an earlier description in the perifornical lateral hypothalamus. Our copy does not compare the control total with prior reports or explicitly describe a distribution across both the lateral and posterior hypothalamus. Page numbers were not available in the indexed passages. (LLM, conf=0.83)
- Partly supportedcites [15] Thannickal TC Lai YY Siegel JM Hypocretin (orexin) cell loss in Parkinson's disease Brain 2007 130 1586 1595 17491094 PMC8762453 sourceExperimental — accuracy not yet measured
The Materials and methods and Quantitative analysis sections say the authors examined five normal brains and determined hypocretin-cell number and distribution. The passages available from our copy do not give a total control-neuron count or say that the count and lateral/posterior hypothalamic distribution were similar to prior reports (pages not provided). (LLM, conf=0.70)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Other reports describe pituitary and hypothalamic dysfunction,17,18”
§ Loss of hypocretin (orexin) neurons with traumatic brain injury > Discussion
What the sources say
- Partly supportedcites [17] Karavitaki N Wass J Henderson Slater JD Wade D A case of post-traumatic isolated ACTH deficiency with spontaneous recovery 9 months after the event J Neurol Neurosurg Psychiatry 2006 77 276 277 16421141 PMC2077606 sourceExperimental — accuracy not yet measured
The case report describes isolated ACTH deficiency after traumatic brain injury, supporting pituitary dysfunction. The Discussion mentions the hypothalamus as a possible site of injury but does not report hypothalamic dysfunction; page numbers are unavailable in our copy. (LLM, conf=0.83)
- Not checked — no full text of the sourcecites [18] Schneider HJ Aimaretti G Kreitschmann-Andermahr I Hypopituitarism Lancet 2007 369 1461 1470 17467517 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Partly supported
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The pattern of gliosis differed across the TBI patients.”
§ Loss of hypocretin (orexin) neurons with traumatic brain injury > Results
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Many hypocretin neurons in TBI patients were small and pyknotic, and the density of hypocretin fibers appeared reduced.”
§ Loss of hypocretin (orexin) neurons with traumatic brain injury > Results
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Among the TBI patients, the number of hypocretin neurons differed moderately between the left and right sides of the hypothalamus and between individuals, reflecting the asymmetry and heterogeneity of TBI.”
§ Loss of hypocretin (orexin) neurons with traumatic brain injury > Results
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, our TBI patients had significantly fewer hypocretin neurons even though they were younger than the controls.”
§ Loss of hypocretin (orexin) neurons with traumatic brain injury > Discussion
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“TBI patients also had 31% fewer MCH neurons than controls (39,540±10,900 vs. 57,176±24,016), but this reduction was not quite statistically significant (p = 0.06), probably because of variable numbers of MCH neurons.”
§ Loss of hypocretin (orexin) neurons with traumatic brain injury > Results
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“If one excludes the female control subject with surprisingly low numbers of MCH neurons (control subject 2), then the TBI subjects had 29% fewer hypocretin neurons than controls (33,342±2,785; p=0.002) and 40% fewer MCH neurons (66,434±18,730; p=0.003).”
§ Loss of hypocretin (orexin) neurons with traumatic brain injury > Results
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The perivascular staining may represent phagocytized hypocretin peptide following damage to the hypocretin neurons.”
§ Loss of hypocretin (orexin) neurons with traumatic brain injury > Results
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“In addition, we did not examine other wake-promoting systems, and the extent of injury to other arousal pathways should be further investigated in larger human and animal studies.”
§ Loss of hypocretin (orexin) neurons with traumatic brain injury > Discussion
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“We examined a small number of brains, and the control subjects were not fully matched.”
§ Loss of hypocretin (orexin) neurons with traumatic brain injury > Discussion
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“One early study showed damage to the hypothalamus in 42% of deceased TBI patients.11”
§ Loss of hypocretin (orexin) neurons with traumatic brain injury > Discussion
What the sources say
- Not checked — no full text of the sourcecites [11] Crompton MR Hypothalamic lesions following closed head injury Brain 1971 94 165 172 5552160 source
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“In this pilot study, the TBI patients were younger (51 ± 19 years) than the controls (69 ± 18 years), and all subjects were male except for one woman in the control group.”
§ Loss of hypocretin (orexin) neurons with traumatic brain injury > Results
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In the paper
“To estimate accurately the numbers of hypocretin and MCH neurons in each section, we performed Abercrombie corrections based on the size of the cell nuclei in each subject.13”
§ Loss of hypocretin (orexin) neurons with traumatic brain injury > Methods > Cell counts
What the sources say
- Not checked — no full text of the sourcecites [13] Guillery RW On counting and counting errors J Comp Neurol 2002 447 1 7 11967890 source
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“Postmortem delays were similar in both groups (TBI: 12±3 hours, controls: 13±3 hours) (Supplemental Table).”
§ Loss of hypocretin (orexin) neurons with traumatic brain injury > Results
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Only clearly-immunolabeled neurons with neuronal morphology, outgoing axons and dendrites, and a nuclear void were counted.”
§ Loss of hypocretin (orexin) neurons with traumatic brain injury > Methods > Cell counts
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“This injury was not limited to the hypocretin neurons as there was a partial loss of neurons producing MCH and patchy gliosis throughout the hypothalamus.”
§ Loss of hypocretin (orexin) neurons with traumatic brain injury > Discussion
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“It is possible that non-fatal TBI is associated with a less severe loss of hypocretin neurons.”
§ Loss of hypocretin (orexin) neurons with traumatic brain injury > Discussion
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“To prevent miscounting, we used a fine-scale counting grid that encompassed no more than 10 neurons per grid sector.”
§ Loss of hypocretin (orexin) neurons with traumatic brain injury > Methods > Cell counts
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Hypersomnolence is common with hypothalamic and rostral brainstem injuries, but is uncommon with selective loss of the hypocretin neurons.21”
§ Loss of hypocretin (orexin) neurons with traumatic brain injury > Discussion
What the sources say
- Not matchedcites [21] Scammell TE Culebras A Secondary Narcolepsy Sleep Disorders and Neurologic Diseases 2007 2nd edition New York Informa Healthcare 117 134
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“About one-third of TBI patients have brainstem injuries, often near the midbrain tegmentum, that may disrupt ascending monoaminergic or cholinergic wake-promoting pathways.20”
§ Loss of hypocretin (orexin) neurons with traumatic brain injury > Discussion
What the sources say
- Not checked — no full text of the sourcecites [20] Crompton MR Brainstem lesions due to closed head injury Lancet 1971 1 669 673 4101614 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“Though TBI brains contained fewer hypocretin neurons, the neurons were distributed in a normal pattern, thus demonstrating the reliability and completeness of the cell counts (Figure 2).”
§ Loss of hypocretin (orexin) neurons with traumatic brain injury > Results
boosteddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“In all subjects, the complete hypocretin neuron field was examined (Supplemental Figure A).”
§ Loss of hypocretin (orexin) neurons with traumatic brain injury > Results
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
The authors state this as an assumption.
Partial loss of hypocretin neurons causes the generally milder sleepiness of narcolepsy without cataplexy and Parkinson's disease.
“some hypothesize that a partial loss of these cells causes the generally milder sleepiness of narcolepsy without cataplexy and Parkinson’s disease.14,15,19”
“This assumption is supported by our recent finding of reduced CSF hypocretin-1 levels in sleepy TBI patients who survived their injury.2”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“Baumann et al. 2009 found that in 4 TBI patients, the number of hypocretin neurons was decreased by 27% compared to controls.47”
From Effects of Traumatic Brain Injury on the Orexin/Hypocretin System (2025) · cites this paper as [47]
The cited source says what the claim attributes to it.
In the citing paper
“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 [47]
Citations
Cites
Narcolepsy in orexin Knockout Mice
Chemelli, R. M., Willie, J. T., Sinton, C. M., Elmquist, J. K., Scammell, T., Lee, C., Richardson, J. A., Williams, S. C., Xiong, Y., Kisanuki, Y., et al. (1999) · Cell · doi:10.1016/s0092-8674(00)81973-x · Cited by 3,095 · cited 1×
“Selective loss of the hypocretin-producing neurons causes sleepiness and cataplexy in 90% of patients with narcolepsy, and identical symptoms occur in mice genetically lacking hypocretins.(10) Injury to the hypothalamus is common in patients with TBI,(11) but its clinical impact remains unclear.”
BackgroundSelf-citationPeyron, C., Faraco, J., Rogers, W., Ripley, B., Overeem, S., Charnay, Y., Nevsimalova, S., Aldrich, M., Reynolds, D., Albin, R., et al. (2000) · Nature Medicine · doi:10.1038/79690 · Cited by 2,118 · cited 1×
“In controls, the total number of hypocretin neurons and their distribution across the lateral and posterior hypothalamus were similar to prior reports.(7,8,14,15) Hypothalami from TBI patients also contained intense perivascular hypocretin immunoreactivity (Fig 3).”
ResultReduced Number of Hypocretin Neurons in Human Narcolepsy
Thannickal, T. C., Moore, R. Y., Nienhuis, R., Ramanathan, L., Gulyani, S., Aldrich, M., Cornford, M., & Siegel, J. M. (2000) · Neuron · doi:10.1016/s0896-6273(00)00058-1 · Cited by 2,089
Neural substrates of awakening probed with optogenetic control of hypocretin neurons
Adamantidis, A. R., Zhang, F., Aravanis, A. M., Deisseroth, K., & de Lecea, L. (2007) · Nature · doi:10.1038/nature06310 · Cited by 1,341
Incidence of Traumatic Brain Injury in the United States, 2003
Rutland-Brown, W., Langlois, J. A., Thomas, K. E., & Xi, Y. L. (2006) · Journal of Head Trauma Rehabilitation · doi:10.1097/00001199-200611000-00009 · Cited by 836
Hypocretin (orexin) cell loss in Parkinson's disease
Thannickal, T. C., Lai, Y.-Y., & Siegel, J. M. (2007) · Brain · doi:10.1093/brain/awm097 · Cited by 566 · cited 2×
“Clearly, extensive loss of hypocretin neurons is sufficient to cause the sleepiness of narcolepsy with cataplexy, and some hypothesize that a partial loss of these cells causes the generally milder sleepiness of narcolepsy without cataplexy and Parkinson disease.(14,15,19) This assumption is supported by our recent fi…”
ResultHypocretin (orexin) loss in Parkinson's disease
Fronczek, R., Overeem, S., Lee, S. Y. Y., Hegeman, I. M., van Pelt, J., van Duinen, S. G., Lammers, G. J., & Swaab, D. F. (2007) · Brain · doi:10.1093/brain/awm090 · Cited by 463 · cited 2×
“Clearly, extensive loss of hypocretin neurons is sufficient to cause the sleepiness of narcolepsy with cataplexy, and some hypothesize that a partial loss of these cells causes the generally milder sleepiness of narcolepsy without cataplexy and Parkinson disease.(14,15,19) This assumption is supported by our recent fi…”
ResultHassani, O. K., Lee, M. G., & Jones, B. E. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0811400106 · Cited by 451 · cited 1×
“Loss of the MCH neurons may also contribute to the pathophysiology of post-traumatic sleep-wake disturbances, as these cells are hypothesized to regulate rapid eye movement sleep.(22,23) Overall, it seems likely that the persistent sleepiness in some TBI patients is due to a combination of reduced hypocretin signaling…”
BackgroundSleep-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 · cited 7×
“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…”
BackgroundMethodResultInfluentialSelf-citationOn counting and counting errors
Guillery, R. W. (2002) · Journal of Comparative Neurology · doi:10.1002/cne.10221 · Cited by 343 · cited 1×
“To estimate accurately the numbers of hypocretin and MCH neurons in each section, we performed Abercrombie corrections based on the size of the cell nuclei in each subject.(13) We then calculated the total numbers of hypocretin and MCH neurons by multiplying the cell counts per section by the section sampling frequenc…”
Method
Cited by
Sorted by citations
Control of sleep and wakefulness
Brown, R. E., Basheer, R., McKenna, J. T., Strecker, R. E., & McCarley, R. W. (2012) · Physiological Reviews · doi:10.1152/physrev.00032.2011 · Cited by 1,477
Narcolepsy — clinical spectrum, aetiopathophysiology, diagnosis and treatment
Bassetti, C. L., Adamantidis, A., Burdakov, D., Han, F., Gay, S., Kallweit, U., Khatami, R., Koning, F., Kornum, B. R., Lammers, G. J., et al. (2019) · Nature Reviews Neurology · doi:10.1038/s41582-019-0226-9 · Cited by 679
Self-citationOrexin Receptors: Pharmacology and Therapeutic Opportunities
Scammell, T. E., & Winrow, C. J. (2011) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010510-100528 · Cited by 391
Self-citationSleep Neurobiology from a Clinical Perspective
España, R. A., & Scammell, T. E. (2011) · SLEEP · doi:10.5665/sleep.1112 · Cited by 294
Self-citationSleep disturbance and melatonin levels following traumatic brain injury
Shekleton, J. A., Parcell, D. L., Redman, J. R., Phipps‐Nelson, J., Ponsford, J. L., & Rajaratnam, S. M. W. (2010) · Neurology · doi:10.1212/wnl.0b013e3181e0438b · Cited by 248
Ponsford, J. L., Ziino, C., Parcell, D. L., Shekleton, J. A., Roper, M., Redman, J. R., Phipps‐Nelson, J., & Rajaratnam, S. M. W. (2012) · Journal of Head Trauma Rehabilitation · doi:10.1097/htr.0b013e31824ee1a8 · Cited by 235
Sleep-wake disturbances after traumatic brain injury
Ouellet, M.-C., Beaulieu-Bonneau, S., & Morin, C. M. (2015) · The Lancet Neurology · doi:10.1016/s1474-4422(15)00068-x · Cited by 231
Sleep-wake disturbances 3 years after traumatic brain injury
Kempf, J., Werth, E., Kaiser, P. R., Bassetti, C. L., & Baumann, C. R. (2010) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.2009.201913 · Cited by 207
“In a recent pilot study, we found a significant decrease of neurons producing the wake-promoting neurotransmitter hypocretin (orexin) in the hypothalamus of deceased TBI patients, when compared with controls.(15) This loss and other structural changes in sleepewake regulations neuronal systems might contribute to slee…”
BackgroundSelf-citationSleep-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
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
“Both studies implicated deficits in the orexin system, which is consistent with the destabilization of waking during the active period [174].”
BackgroundWickwire, E. M., Williams, S. G., Roth, T. G., Capaldi, V. F., Jaffe, M., Moline, M. L., Motamedi, G. K., Morgan, G. W., Mysliwiec, V., Germain, A., et al. (2016) · Neurotherapeutics · doi:10.1007/s13311-016-0429-3 · Cited by 172
Modafinil 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
Self-citationGrima, N., Rajaratnam, S. M. W., Mansfield, D. R., Sletten, T. L., Spitz, G., & Ponsford, J. L. (2018) · BMC Medicine · doi:10.1186/s12916-017-0995-1 · Cited by 149
“While melatonin was found to be effective in alleviating sleep disturbances, it is acknowledged that the mechanisms underpinning sleep disturbances in TBI involve multiple biological and psychological systems, such as alterations in monoaminergic neurons [45, 46] and wake-promoting hypocretin-1 neurons [47], and alter…”
BackgroundImbach, L. L., Valko, P. O., Li, T., Maric, A., Symeonidou, E.-R., Stover, J. F., Bassetti, C. L., Mica, L., Werth, E., & Baumann, C. R. (2015) · Brain · doi:10.1093/brain/awu391 · Cited by 142
“However, fatal TBI is associated with a partial loss of wake-promoting hypocretin (orexin)- and histamine-producing neurons (Baumann et al., 2009; Valko et al., 2014).”
BackgroundSelf-citationNarcolepsy: Neural Mechanisms of Sleepiness and Cataplexy
Burgess, C. R., & Scammell, T. E. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.2630-12.2012 · Cited by 139
“, 2007) and traumatic brain injury (Baumann et al., 2009), disorders that often produce sleepiness but no cataplexy.”
Self-citationSleep disorders, obesity, and aging: The role of orexin
Nixon, J. P., Mavanji, V., Butterick, T. A., Billington, C. J., Kotz, C. M., & Teske, J. A. (2014) · Ageing Research Reviews · doi:10.1016/j.arr.2014.11.001 · Cited by 137
Sleep disturbances, TBI and PTSD: Implications for treatment and recovery
Stavitsky, K., Kark, S. M., Gehrman, P., & Bogdanova, Y. (2015) · Clinical Psychology Review · doi:10.1016/j.cpr.2015.05.008 · Cited by 143
“Low cerebrospinal fluid (CSF) hypocretin (orexin) has been reported in patients following TBI (Baumann et al., 2009; Baumann et al., 2005).”
BackgroundSleep Disturbances in Traumatic Brain Injury: A Meta-Analysis
Grima, N., Ponsford, J. L., Rajaratnam, S. M. W., Mansfield, D. R., & Pase, M. P. (2016) · Journal of Clinical Sleep Medicine · doi:10.5664/jcsm.5598 · Cited by 121
“Postmortem investigations in TBI patients have identified significant reductions in wake-promoting hypocretin 53 and histaminergic neuronal populations, 54 which may underpin increased sleep drive.”
Semple, B. D., Zamani, A., Rayner, G., Shultz, S. R., & Jones, N. C. (2018) · Neurobiology of Disease · doi:10.1016/j.nbd.2018.07.018 · Cited by 126
Wickwire, E. M., Schnyer, D. M., Germain, A., Smith, M. T., Williams, S. G., Lettieri, C. J., McKeon, A. B., Scharf, S. M., Stocker, R., Albrecht, J. S., et al. (2018) · Journal of Neurotrauma · doi:10.1089/neu.2017.5243 · Cited by 112
Self-citationBrown, J. A., Woodworth, H. L., & Leinninger, G. M. (2015) · Frontiers in Systems Neuroscience · doi:10.3389/fnsys.2015.00009 · Cited by 106
“OX neurons are also reduced after traumatic brain injury, which similarly results in chronic daytime sleepiness and reduced locomotor activity (Baumann et al., 2005, 2009; Willie et al., 2012).”
BackgroundChristensen, J., Yamakawa, G. R., Shultz, S. R., & Mychasiuk, R. (2020) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2020.101917 · Cited by 110
Piantino, J. A., Lim, M. M., Newgard, C. D., & Iliff, J. J. (2019) · Current Pain and Headache Reports · doi:10.1007/s11916-019-0799-4 · Cited by 98
Changes in Sleep Patterns Following Traumatic Brain Injury
Ponsford, J. L., Parcell, D. L., Sinclair, K. L., Roper, M., & Rajaratnam, S. M. W. (2013) · Neurorehabilitation and neural repair · doi:10.1177/1545968313481283 · Cited by 98
“It also supports the contention that hypersomnia occurs following TBI, possibly caused by a loss of hypocretin neurons.(13,14,18,19) Recent studies have also found lower levels of evening melatonin in people with TBI, which may contribute to the increased sleep onset latency and nighttime awakenings.”
BackgroundInflammatory Signaling in Post-Stroke Fatigue and Depression
Wen, H., Weymann, K. B., Wood, L. J., & Wang, Q. M. (2018) · European Neurology · doi:10.1159/000494988 · Cited by 95
Wallace, D. M., Shafazand, S., Ramos, A. R., Carvalho, D. Z., Gardener, H., Lorenzo, D., & Wohlgemuth, W. K. (2011) · Sleep Medicine · doi:10.1016/j.sleep.2011.06.004 · Cited by 83
“As most of our patients presented with multiple and mixed aetiology head injury, it is conceivable that damage to the hypothalamus with loss of hypocretin neurons and damage to other diffusely distributed arousal systems may have occurred as a consequence of shear stress/diffuse axonal injury sometimes seen in closed…”
BackgroundPain and sleep in post-concussion/mild traumatic brain injury
Lavigne, G. J., Khoury, S., Chauny, J., & Désautels, A. (2015) · Pain · doi:10.1097/j.pain.0000000000000111 · Cited by 88
“This was associated with hypocretin (Hcrt; orexin) reduction; Hcrt is a neuropeptide essential for maintaining consolidated sleep/ wake states.(10,11,130) No single gene can explain the complex interrelations between”
BackgroundA Model of Fatigue Following Traumatic Brain Injury
Ponsford, J. L., Schönberger, M., & Rajaratnam, S. M. W. (2014) · Journal of Head Trauma Rehabilitation · doi:10.1097/htr.0000000000000049 · Cited by 82
Excessive sleep need following traumatic brain injury: a case–control study of 36 patients
Sommerauer, M., Valko, P. O., Werth, E., & Baumann, C. R. (2013) · Journal of Sleep Research · doi:10.1111/jsr.12068 · Cited by 83
“Accordingly, we found partial loss of hypocretin neurones in the hypothalamus of deceased TBI patients (Baumann et al., 2009).”
BackgroundSelf-citationSleep–wake disorders persist 18 months after traumatic brain injury but remain underrecognized
Imbach, L., Büchele, F., Valko, P. O., Li, T., Maric, A., Stover, J., Bassetti, C. L., Mica, L., Werth, E., & Baumann, C. R. (2016) · Neurology · doi:10.1212/wnl.0000000000002697 · Cited by 76
“In this line, we hypothesize that any type of TBI could induce damage to highly vulnerable sleep-relevant cerebral centers.(16,17) However, we cannot rule out that other factors contribute to chronic posttraumatic pleiosomnia, and further studies are needed to improve our understanding of the pathophysiologic mechanis…”
BackgroundSelf-citationPrevalence and predictors of fatigue in glioblastoma: a prospective study
Valko, P. O., Siddique, A., Linsenmeier, C., Zaugg, K., Held, U., & Höfer, S. (2014) · Neuro-Oncology · doi:10.1093/neuonc/nou127 · Cited by 74
Self-citationWillie, J. T., Lim, M. M., Bennett, R. E., Azarion, A. A., Schwetye, K. E., & Brody, D. L. (2012) · Journal of Neurotrauma · doi:10.1089/neu.2012.2404 · Cited by 79
“Furthermore, an autopsy study demonstrated significant reduction of orexin neurons in brains obtained following lethal TBI compared with control brains (Baumann et al., 2009).”
InfluentialValko, P. O., Gavrilov, Y. V., Yamamoto, M., Finn, K., Reddy, H., Haybaeck, J., Weis, S., Scammell, T. E., & Baumann, C. R. (2015) · Annals of Neurology · doi:10.1002/ana.24298 · Cited by 78
“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-citationSkopin, M. D., Kabadi, S. V., Viechweg, S. S., Mong, J. A., & Faden, A. I. (2015) · Journal of Neurotrauma · doi:10.1089/neu.2014.3664 · Cited by 71
“Clinical studies have observed increases in hypersomnia such as excessive daytime sleepiness (EDS) in approximately 25% of patients with TBI.5,6 Other retrospective studies indicate that approximately half of the patients experience some form of EDS with half of those having severe hypersomnia.5,6 Fur- ther, changes i…”
BackgroundInfluentialBassetti, C. L., Ferini‐Strambi, L., Brown, S. A., Adamantidis, A., Benedetti, F., Bruni, O., Cajochen, C., Dolenc‐Grošelj, L., Ferri, R., Gais, S., et al. (2015) · European Journal of Neurology · doi:10.1111/ene.12781 · Cited by 75
“Related research suggested a role of impaired hypocretin neurotransmission in other neuropsychiatric disorders such as head trauma, Parkinson’s disease and Alzheimer’s disease and improvement of insomnia following antagonization of the hypocretin system [19,41,66,67].”
BackgroundSelf-citationTraumatic Brain Injury and Disturbed Sleep and Wakefulness
Baumann, C. R. (2012) · NeuroMolecular Medicine · doi:10.1007/s12017-012-8178-x · Cited by 66
“1) (Baumann et al. 2009).”
Self-citationBowirrat, A., Chen, T. J. H., Blum, K., Madigan, M. A., Bailey, J. A., Chen, A. L. C., Downs, B. W., Braverman, E. R., Shahien, R., Waite, R. L., et al. (2010) · Current Neuropharmacology · doi:10.2174/157015910793358123 · Cited by 70
Traumatic Brain Injury and Incidence Risk of Sleep Disorders in Nearly 200,000 US Veterans
Leng, Y., Byers, A. L., Barnes, D. E., Peltz, C. B., Li, Y., & Yaffe, K. S. (2021) · Neurology · doi:10.1212/wnl.0000000000011656 · Cited by 65
“For instance, hypothalamic injury could contribute to sleep-wake disorders through loss of wake-promoting histaminergic or orexin/hypocretin neurons.(41,42) Risk of sleep apnea might be increased as a result of mechanical changes of craniofacial anatomy, although the exact pathways linking TBI and different forms of s…”
BackgroundGreen, T. R. F., Ortiz, J. B., Wonnacott, S., Williams, R. J., & Rowe, R. K. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.00894 · Cited by 68
“Extensive loss of orexin neurons and consequent excessive daytime sleepiness have been observed both pre-clinically and clinically after TBI (Baumann et al., 2009; Thomasy et al., 2017; Thomasy and Opp, 2019).”
BackgroundIntrathecal Baclofen Associated With Improvement of Consciousness Disorders in Spasticity Patients
Margetis, K. D., Korfias, S. I., Gatzonis, S. D., Boutos, N., Stranjalis, G., Boviatsis, E., & Sakas, D. E. (2013) · Neuromodulation Technology at the Neural Interface · doi:10.1111/ner.12147 · Cited by 63
“The above data taken together with the fact that severe TBI can result in loss of orexin neurons (24) support the notion that ITB can modulate a damaged orexin pathway in brain-injured patients.”
Almorexant Promotes Sleep and Exacerbates Cataplexy in a Murine Model of Narcolepsy
Wurts, S. W., Morairty, S. R., Fisher, S. P., Chen, T.-M., Warrier, D. R., & Kilduff, T. S. (2013) · SLEEP · doi:10.5665/sleep.2442 · Cited by 60
Sleep Quantity and Quality during Acute Concussion: A Pilot Study
Raikes, A. C., & Schaefer, S. Y. (2016) · SLEEP · doi:10.5665/sleep.6314 · Cited by 64
Hou, L., Han, X., Sheng, P. X., Tong, W., Li, Z., Xu, D., Yu, M., Huang, L., Zhao, Z., Yi-cheng, L., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0076087 · Cited by 62
“revealed reduced number of hypothalamic hypocretin (orexin) neurons in patients who died of severe TBI, low and undetectable cerebrospinal fluid levels of hypocretin (orexin) in the acute period after TBI and an association between low hypocretion levels and posttraumatic sleepiness [14,35,36].”
BackgroundBüchele, F., Morawska, M. M., Schreglmann, S. R., Penner, M., Muser, M. H., Baumann, C. R., & Noaín, D. (2015) · Journal of Neurotrauma · doi:10.1089/neu.2015.4001 · Cited by 54
“15,16 To better understand the link between histological damage and SWD after TBI, we need an appropriate experimental rodent TBI model that both replicates human patterns of histological as well as behavioral sequelae and allows for long-term recordings of sleep-wake states.”
Self-citationActigraphic Assessment of Sleep Disturbances following Traumatic Brain Injury
Sinclair, K. L., Ponsford, J. L., & Rajaratnam, S. M. W. (2012) · Behavioral Sleep Medicine · doi:10.1080/15402002.2012.726203 · Cited by 53
“Reductions in both hypocretin (Baumann et al., 2009; Baumann et al., 2005; Baumann et al., 2007) and melatonin (Shekleton, Parcell, Redman, Ponsford, & Rajaratnam, 2010), have been reported in TBI groups.”
BackgroundElliott, J. E., De Luche, S. E., Churchill, M. J., Moore, C., Cohen, A. S., Meshul, C. K., & Lim, M. M. (2018) · Sleep · doi:10.1093/sleep/zsx212 · Cited by 63
“compared with noninjured control brains [41].”
Cortical Excitability Changes in Patients with Sleep-Wake Disturbances after Traumatic Brain Injury
Nardone, R., Bergmann, J., Kunz, A. B., Caleri, F., Seidl, M., Tezzon, F., Gerstenbrand, F., Trinka, E., & Golaszewski, S. M. (2011) · Journal of Neurotrauma · doi:10.1089/neu.2010.1748 · Cited by 49
Sabir, 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
“Alternatively, these changes may be linked to alterations in other neuronal circuits involved in sleep-wake regulation, such as hypothalamic orexin neurons or the thalamic reticular nucleus that were both shown to be modified by TBI (Baumann et al., 2009; Hazra et al., 2014; Willie et al., 2012).”
BackgroundSleep and Fatigue Following Traumatic Brain Injury
Ponsford, J. L., & Sinclair, K. L. (2014) · Psychiatric Clinics of North America · doi:10.1016/j.psc.2013.10.001 · Cited by 49
Babiloni, A. H., Baril, A., Charlebois‐Plante, C., Jodoin, M., Sanchez, E., Baets, L. D., Arbour, C., Lavigne, G. J., Gosselin, N., & Beaumont, L. D. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12051793 · Cited by 47
“Another sleep-related consequence of TBI is increased sleepiness, especially in early stages, and research has highlighted the damage of orexin/hypocretin neurons, whose activation involve wakefulness, as a possible contributor of the association between this association [68].”
BackgroundRaikes, A. C., Bajaj, S., Dailey, N. S., Smith, R. S., Alkozei, A., Satterfield, B. C., & Killgore, W. D. S. (2018) · Frontiers in Neurology · doi:10.3389/fneur.2018.00468 · Cited by 43
Sleep Disorders Associated With Traumatic Brain Injury—A Review
Singh, K., Morse, A. M., Tkachenko, N., & Kothare, S. V. (2016) · Pediatric Neurology · doi:10.1016/j.pediatrneurol.2016.02.013 · Cited by 44
Sleep Disturbances in Traumatic Brain Injury: Associations With Sensory Sensitivity
Elliott, J. E., Opel, R. A., Weymann, K. B., Chau, A. Q., Papesh, M. A., Callahan, M. L., Storzbach, D. M., & Lim, M. M. (2018) · Journal of Clinical Sleep Medicine · doi:10.5664/jcsm.7220 · Cited by 43
“These included determining (1) the number of TBIs; (2) the recency of the subjects’ TBI (determined from year of most recent TBI if > 1 TBI was identified); (3) whether or not the TBI(s) was caused by blast exposure; (4) whether the TBI caused loss of consciousness, confusion, posttraumatic amnesia, or postconcussive…”
Sleep disorders in traumatic brain injury
Wolfe, L. F., Sahni, A., & Attarian, H. P. (2018) · Neurorehabilitation · doi:10.3233/nre-182583 · Cited by 40
Adeghate, E. A., Fernández-Cabezudo, M. J., Rashed, H., et al. (2010) · PLoS ONE · doi:10.1371/journal.pone.0008587 · Cited by 40
“Founder orexin deficient (OX) mice were on a C57BL/6J-129/SvEV background, and their offspring were backcrossed with C57BL/6J mice for 6–8 generations [25].”
MethodThe Trouble with Tribbles: Do Antibodies Against TRIB2 Cause Narcolepsy?
Lim, A. S. P., & Scammell, T. E. (2010) · SLEEP · doi:10.1093/sleep/33.7.857 · Cited by 39
Self-citationBrain interrupted: Early life traumatic brain injury and addiction vulnerability
Cannella, L. A., McGary, H. M., & Ramirez, S. H. (2019) · Experimental Neurology · doi:10.1016/j.expneurol.2019.03.003 · Cited by 42
A review of sleep disturbances following traumatic brain injury
Zuzuárregui, J. R. P., Bickart, K. C., & Kutscher, S. J. (2018) · Sleep Science and Practice · doi:10.1186/s41606-018-0020-4 · Cited by 39
Sleep disorders in children with traumatic brain injury: a case of serious neglect
Stores, G., & Stores, R. (2013) · Developmental Medicine & Child Neurology · doi:10.1111/dmcn.12163 · Cited by 36
Hypocretin Mediates Sleep and Wake Disturbances in a Mouse Model of Traumatic Brain Injury
Thomasy, H. E., & Opp, M. R. (2019) · Journal of Neurotrauma · doi:10.1089/neu.2018.5810 · Cited by 35
“Hypocre-tin, 37,38,45,46 histamine, 36,44 serotonin, 49 noradrenaline, 49 acetylcholine, 37,47,73 and melatonin 50 are the transmitters for which data suggest potential roles as mediators of post-TBI sleep and wake disturbances.”
Markovic, S. J., Fitzgerald, M., Peiffer, J. J., Scott, B. R., Rainey‐Smith, S. R., Sohrabi, H. R., & Brown, B. M. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101322 · Cited by 37
Thomasy, H. E., Febinger, H. Y., Ringgold, K. M., Gemma, C., & Opp, M. R. (2017) · Neurobiology of Sleep and Circadian Rhythms · doi:10.1016/j.nbscr.2016.03.001 · Cited by 37
“Furthermore, the number of hypocretin neurons are reduced in post-mortem brains of patients who died from TBI (Baumann et al., 2009).”
BackgroundInfluentialNeuropathological investigation of hypocretin expression in brains of dementia with Lewy bodies
Kasanuki, K., Iseki, E., Kondo, D., et al. (2014) · Neuroscience Letters · doi:10.1016/j.neulet.2014.03.020 · Cited by 34
Vu, P. A., Tucker, L. B., Liu, J., McNamara, E. H., Tran, T., Fu, A. H., Kim, Y., & McCabe, J. T. (2018) · Brain Research · doi:10.1016/j.brainres.2018.08.034 · Cited by 32
Acute Post-Traumatic Sleep May Define Vulnerability to a Second Traumatic Brain Injury in Mice
Rowe, R. K., Harrison, J. L., Morrison, H. W., Subbian, V., Murphy, S. M., & Lifshitz, J. (2019) · Journal of Neurotrauma · doi:10.1089/neu.2018.5980 · Cited by 34
Lu, W. Y.-R., Krellman, J. W., & Dijkers, M. P. J. M. (2016) · Neurorehabilitation · doi:10.3233/nre-151296 · Cited by 39
“TBI can damage neural regions that subserve sleep regulation, including the suprachiasmatic nucleus, hypothalamus, midbrain, and ascending reticular activating system (Baumann et al., 2009; Frieboes et al., 1999), with associated alterations in the level of neurotransmitters such as hypocretin-1 (Baumann, Werth, Stock…”
BackgroundGao, X., & Hermes, G. (2015) · Frontiers in Systems Neuroscience · doi:10.3389/fnsys.2015.00142 · Cited by 31
“Therefore, it is reasonable to postulate that hypocretin neurons may undergo some plastic changes during intensive activation according to Hebbian theory.”
BackgroundExpression and Localization of the Orexin-1 Receptor (OX1R) After Traumatic Brain Injury in Mice
Mihara, Y., Dohi, K., Yofu, S., Nakamachi, T., Ohtaki, H., Shioda, S., & Aruga, T. (2011) · Journal of Molecular Neuroscience · doi:10.1007/s12031-010-9438-6 · Cited by 31
Traumatic Head Injury in Cluster Headache: Cause or Effect?
Lambru, G., & Matharu, M. S. (2012) · Current Pain and Headache Reports · doi:10.1007/s11916-012-0248-0 · Cited by 27
“[46] have shown selective injury and loss of hypocretin-producing neurons in the posterolateral hypothalamus in people with severe brain injury, possibly explaining the excessive daytime sleepiness of these patients.”
BackgroundMelanin concentrating hormone in central hypersomnia
Peyron, C., Valentin, F., Bayard, S., Hanriot, L., Bedetti, C., Rousset, B., Luppi, P., & Dauvilliers, Y. A. (2011) · Sleep Medicine · doi:10.1016/j.sleep.2011.04.002 · Cited by 26
“This observation seems of major interest since histological data recently reported a 30% loss of MCH neurons in patients with traumatic brain injury [28].”
BackgroundDiagnosis and Management of Narcolepsy
Schneider, L. D., & Mignot, E. J.-M. (2017) · Seminars in Neurology · doi:10.1055/s-0037-1605554 · Cited by 26
Neurobiology of Arousal and Sleep: Updates and Insights Into Neurological Disorders
Lim, M. M., & Szymusiak, R. S. (2015) · Current Sleep Medicine Reports · doi:10.1007/s40675-015-0013-0 · Cited by 26
Yamakawa, G. R., Brady, R. D., Sun, M., McDonald, S. J., Shultz, S. R., & Mychasiuk, R. (2020) · Neurobiology of Sleep and Circadian Rhythms · doi:10.1016/j.nbscr.2020.100058 · Cited by 27
“Autopsied brain tissue from patients with severe TBI showed significant loss of hypothalamic orexin neurons (Baumann et al., 2009).”
BackgroundMachaalani, R., Hunt, N. J., & Waters, K. A. (2013) · Brain Research · doi:10.1016/j.brainres.2013.06.035 · Cited by 27
Targets for migraine treatment: beyond calcitonin gene-related peptide
Moreno‐Ajona, D., Villar‐Martínez, M. D., & Goadsby, P. J. (2021) · Current Opinion in Neurology · doi:10.1097/wco.0000000000000935 · Cited by 25
Sleep complications following traumatic brain injury
Grima, N., Ponsford, J. L., & Pase, M. P. (2017) · Current Opinion in Pulmonary Medicine · doi:10.1097/mcp.0000000000000429 · Cited by 25
Clinical Approach to Commonly Encountered Problems
Hines, M. T. (2017) · Elsevier eBooks · doi:10.1016/b978-0-323-44329-6.00007-3 · Cited by 31
Yassin, W., Sugihara, G., Oishi, N., Kubota, M., Ubukata, S., Murai, T., & Ueda, K. (2015) · Journal of Clinical Sleep Medicine · doi:10.5664/jcsm.4710 · Cited by 22
Haynes, Z. A., Collen, J. F., Poltavskiy, E. A., Walker, L. E., Janak, J. C., Howard, J. T., Werner, J. K., Wickwire, E. M., Holley, A. B., Zarzabal, L. A., et al. (2021) · Journal of Clinical Sleep Medicine · doi:10.5664/jcsm.9276 · Cited by 20
“33,34 Sleep-wake disturbances have been reported in up to 85% of patients with TBI in prior studies, and this population is known to have higher rates of insomnia diagnoses.”
El-Khatib, H., Arbour, C., Sanchez, E., Dumont, M., Duclos, C., Blais, H., Carrier, J., Paquet, J., & Gosselin, N. (2018) · Sleep Medicine · doi:10.1016/j.sleep.2018.11.012 · Cited by 20
“maintaining this sleep-wake pattern during the chro nic stage of TBI [15,36].”
BackgroundRowe, R. K., & Griesbach, G. S. (2022) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2022.04.017 · Cited by 21
Lu, W. Y.-R., Cantor, J. B., Aurora, R. N., Gordon, W. A., Krellman, J. W., Nguyen, M., Ashman, T. A., Spielman, L. A., & Ambrose, A. F. (2015) · Brain Injury · doi:10.3109/02699052.2015.1043947 · Cited by 19
“that previous work suggests that at least some individuals with TBI exhibit a hypocretin (orexin) deficiency due to loss of hypocretin-producing neurons, which play an important role in promoting wakefulness [48].”
BackgroundNew insights in post-traumatic headache with cluster headache phenotype: a cohort study
Grangeon, L., O’Connor, E., Chan, C.-K., et al. (2020) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp-2019-322725 · Cited by 19
Adeghate, E. A. (2012) · Vitamins and hormones · doi:10.1016/b978-0-12-394623-2.00007-x · Cited by 19
Elliott, J. E., McBride, A. A., Balba, N. M., Thomas, S. V., Pattinson, C. L., Morasco, B. J., Wilkerson, A. M., Gill, J., & Lim, M. M. (2022) · PLoS ONE · doi:10.1371/journal.pone.0262955 · Cited by 19
Feng, Z., Zhong, Y.-J., Wang, L., et al. (2015) · Neural Regeneration Research · doi:10.4103/1673-5374.155433 · Cited by 18
“It has been reported that orexin was reduced in cerebrospinal fluid in 95% of patients during 2 months after traumatic brain injury, and led to narcolepsy (Baumann et al., 2009; Ramanjaneya et al., 2009; Jeter et al., 2013).”
BackgroundRecovery from Coma Post-Cardiac Arrest Is Dependent on the Orexin Pathway
Kang, Y., Tian, G., Bazrafkan, A. K., Farahabadi, M. H., Azadian, M. M., Abbasi, H., Shamaoun, B. E., Steward, O., & Akbari, Y. (2017) · Journal of Neurotrauma · doi:10.1089/neu.2016.4852 · Cited by 18
Du, M. K., Hunt, N. J., Waters, K. A., & Machaalani, R. (2015) · International Journal of Developmental Neuroscience · doi:10.1016/j.ijdevneu.2015.10.007 · Cited by 19
“Yet, in traumatic brain injury or extreme HH, there was a 3-fold loss of Ox neuropeptide (Baumann et al., 2009).”
BackgroundBotchway-Commey, E. N., Godfrey, C., Anderson, V. A., Nicholas, C. L., & Catroppa, C. (2018) · Journal of Neurotrauma · doi:10.1089/neu.2018.5743 · Cited by 17
“16,17 One theory on the etiology of SWD attributes insomnia to failure of the filtering mechanism used by the corticothalamocortical loop to prevent excitatory inputs from reaching the cortex during sleep.”
Sleep in Traumatic Brain Injury
Vermaelen, J., Greiffenstein, P. P., & deBoisblanc, B. P. (2015) · Critical Care Clinics · doi:10.1016/j.ccc.2015.03.012 · Cited by 16
Secondary Narcolepsy in Children
Madan, R., Pitts, J., Patterson, M. C., et al. (2020) · Journal of Child Neurology · doi:10.1177/0883073820954617 · Cited by 16
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
“Finally, there have been reports of the loss of arousal-promoting orexin/hypocretin neurons as well as other hypothalamic arousal-modulating cells (e.g., histamine and melanin-concentrating hormone) in TBI patients (Baumann et al., 2009; Valko et al., 2015).”
Excessive daytime sleepiness after traumatic brain injury
Crichton, T., Singh, R. K., Abosi-Appeadu, K., & Dennis, G. (2020) · Brain Injury · doi:10.1080/02699052.2020.1810316 · Cited by 19
Palomba, M. L., Etet, P. F. S., & Veronesi, C. (2014) · Neuroscience Letters · doi:10.1016/j.neulet.2014.03.069 · Cited by 17
Traumatic Brain Injury and Behavior
McGee, J. C., Alekseeva, N., Chernyshev, O. Y., & Minagar, A. (2015) · Neurologic Clinics · doi:10.1016/j.ncl.2015.08.004 · Cited by 15
Mild Traumatic Brain Injury Affects Orexin/Hypocretin Physiology Differently in Male and Female Mice
Somach, R. T., Jean, I. D., Farrugia, A. M., & Cohen, A. S. (2023) · Journal of Neurotrauma · doi:10.1089/neu.2023.0125 · Cited by 13
Increased dopaminergic function in the thalamus is associated with excessive daytime sleepiness.
Yousaf, T., Pagano, G., Niccolini, F., & Politis, M. (2017) · Sleep Medicine · doi:10.1016/j.sleep.2017.11.1137 · Cited by 12
“18 neurons in the hypothalamus [50], cholinergic neuro ns in the basal forebrain and serotoninergic neurons in the raphe [51].”
BackgroundThe orexin/hypocretin system in neuropsychiatric disorders: Relation to signs and symptoms
Fronczek, R., Schinkelshoek, M. S., Shan, L., & Lammers, G. J. (2021) · Handbook of clinical neurology · doi:10.1016/b978-0-12-820107-7.00021-5 · Cited by 14
Potential for the development of light therapies in mild traumatic brain injury
Raikes, A. C., & Killgore, W. D. S. (2018) · Concussion · doi:10.2217/cnc-2018-0006 · Cited by 13
Narcolepsy and traumatic brain injury: Cause or consequence?
Poryazova, R., Hug, D., & Baumann, C. R. (2011) · Sleep Medicine · doi:10.1016/j.sleep.2011.04.007 · Cited by 12
“After traumatic brain injury (TBI), hypocretin neurons are partially reduced [2], and excessive daytime sleepiness (EDS) belongs to the most common posttraumatic sleep–wake disturbances [3].”
BackgroundSelf-citation
Metadata
- Authors
- Baumann, C. R., Bassetti, C. L., Valko, P. O., Haybaeck, J., Keller, M., Clark, E., Stocker, R., Tolnay, M., & Scammell, T. E.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- University Hospital Zurich (CH)
- Corresponding author
- Baumann, Christian R.
- ORCID
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 2009-10
- Volume
- 66
- Issue
- 4
- Pages
- 555-559
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- PMC
- PMC2770195
- OpenAlex
- W2025705478
- Semantic Scholar
- 1dbac4f5e899ccafddf7329f779db1028a085914
- Cited by
- 185
- References
- 25
- Citations by year
- 2026: 2 · 2025: 8 · 2024: 6 · 2023: 4 · 2022: 13 · 2021: 10 · 2020: 13 · 2019: 11 · 2018: 22 · 2017: 10 · 2016: 10 · 2015: 19 · 2014: 12 · 2013: 10 · 2012: 12
- FWCI
- 5.33
- 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)
- PubMed Central (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- National Institute of Mental Health (R01 MH062589, MH062589)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury Research
- Keywords
- orexin, traumatic brain injury, hypothalamic neurons, narcolepsy, Parkinson's disease, wakefulness
- MeSH terms
- Orexins, Adult, Aged, Aged, 80 and over, Brain Injuries, Cell Count, Female, Humans, Hypothalamus, Male, Middle Aged, Neurons, Neuropeptides, Pilot Projects, Wakefulness, Intracellular Signaling Peptides and Proteins
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