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Cited by 46Vagus Nerve Stimulation ResearchSleep and Wakefulness ResearchTraumatic Brain Injury and Neurovascular Disturbances

Wake-promoting effects of vagus nerve stimulation after traumatic brain injury: upregulation of orexin-A and orexin receptor type 1 expression in the prefrontal cortex

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Feng, Zhen, Dong, Xiao-yang·2018·Neural Regeneration Research
DOI 10.4103/1673-5374.226395PMC PMC5879895
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Abstract

Orexins, produced in the lateral hypothalamus, are important neuropeptides that participate in the sleep/wake cycle, and their expression coincides with the projection area of the vagus nerve in the brain. Vagus nerve stimulation has been shown to decrease the amounts of daytime sleep and rapid eye movement in epilepsy patients with traumatic brain injury. In the present study, we investigated whether vagus nerve stimulation promotes wakefulness and affects orexin expression. A rat model of traumatic brain injury was established using the free fall drop method. In the stimulated group, rats with traumatic brain injury received vagus nerve stimulation (frequency, 30 Hz; current, 1.0 mA; pulse width, 0.5 ms; total stimulation time, 15 minutes). In the antagonist group, rats with traumatic brain injury were intracerebroventricularly injected with the orexin receptor type 1 (OX1R) antagonist SB334867 and received vagus nerve stimulation. Changes in consciousness were observed after stimulation in each group. Enzyme-linked immunosorbent assay, western blot assay and immunohistochemistry were used to assess the levels of orexin-A and OX1R expression in the prefrontal cortex. In the stimulated group, consciousness was substantially improved, orexin-A protein expression gradually increased within 24 hours after injury and OX1R expression reached a peak at 12 hours, compared with rats subjected to traumatic brain injury only. In the antagonist group, the wake-promoting effect of vagus nerve stimulation was diminished, and orexin-A and OX1R expression were decreased, compared with that of the stimulated group. Taken together, our findings suggest that vagus nerve stimulation promotes the recovery of consciousness in comatose rats after traumatic brain injury. The upregulation of orexin-A and OX1R expression in the prefrontal cortex might be involved in the wake-promoting effects of vagus nerve stimulation.

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  • In one study, orexin expression increased in general from 6 to 24 h after injury, with the highest observed expression at 12 h.

    “One study,79 found that orexin expression increased in general from 6 to 24 h after injury, though the highest orexin observed expression in their study was at 12 h after injury.”

    From Effects of Traumatic Brain Injury on the Orexin/Hypocretin System (2025) · cites this paper as [79]

  • Several studies found an increase of orexin receptors compared to sham-injured animals after TBI.

    “Several studies found an increase of orexin receptors compared to sham-injured animals after TBI,75–79,89”

    From Effects of Traumatic Brain Injury on the Orexin/Hypocretin System (2025) · cites this paper as [79]

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Cited by

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Authors
Feng, Z., & Dong, X.-Y.
Affiliations
First Affiliated Hospital of Nanchang University (CN)
Corresponding author
Feng, Zhen
ORCID
Feng, Zhen
Venue
Neural Regeneration Research
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2018
Volume
13
Issue
2
Pages
244
ISSN
1673-5374 (ISSN-L)
DOI
10.4103/1673-5374.226395
PMC
PMC5879895
OpenAlex
W2794221162
Cited by
46
References
1
Citations by year
2026: 2 · 2025: 11 · 2024: 7 · 2023: 7 · 2022: 4 · 2021: 7 · 2020: 6 · 2019: 2
FWCI
1.69
Type
journal article
Language
en
Open access
Licence
cc-by-nc-sa
Locations
  • Neural Regeneration Research (publishedVersion, cc-by-nc-sa)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Life Sciences › Neuroscience › Neurology › Vagus Nerve Stimulation Research
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
  • Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
Keywords
vagus nerve stimulation, traumatic brain injury, orexin-A, prefrontal cortex, wakefulness, consciousness recovery, SB-334867, coma, sleep-wake cycle

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