Wakefulness-Promoting Effects of Lateral Hypothalamic Area–Deep Brain Stimulation in Traumatic Brain Injury-Induced Comatose Rats: Upregulation of α1-Adrenoceptor Subtypes and Downregulation of Gamma-Aminobutyric Acid β Receptor Expression Via the Orexins Pathway
Abstract
Objective Previous studies have shown that deep brain stimulation (DBS) can improve the level of consciousness of comatose patients with traumatic brain injuries (TBIs). However, the most suitable targets for DBS are unknown, and the mechanisms underlying recovery remain to be determined. The aim of the present study was to assess the effects of lateral hypothalamic area-DBS (LHA-DBS) in comatose rats with TBIs. Methods A total of 55 Sprague-Dawley rats were randomly assigned to 5 groups: the control group, TBI group, stimulated (TBI+LHA-DBS) group, antagonist (TBI+SB334867+LHA-DBS) group, and antagonist control (TBI+saline+LHA-DBS) group. The rats in the control group had undergone a sham operation and anesthesia, without coma induction. Coma was induced using a free-fall drop method. The rats in the stimulated group received bilateral LHA stimulation (frequency, 200 Hz; voltage, 2-4 V; pulse width, 0.1 ms) for 1 hour, with 5-minute intervals between subsequent stimulations, which were applied alternately to the left and right sides of the lateral hypothalamus. The comatose rats in the antagonist group received an intracerebroventricular injection with an orexins receptor type 1 (OX1R) antagonist (SB334867) and then received LHA-DBS. A I-VI consciousness scale and electroencephalography were used to assess the level of consciousness in each group of rats after LHA-DBS. Western blotting and immunofluorescence were used to detect OX1R expression in the LHA and α1-adrenoceptor…
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One study reports a decrease of orexin receptors soon after injury.
“In one study,91 reports a decrease of orexin receptors soon after injury”
From Effects of Traumatic Brain Injury on the Orexin/Hypocretin System (2025) · cites this paper as [91]
Other studies found a decrease of orexin receptors compared to sham-injured animals after TBI.
“while other studies found a decrease of orexin receptors compared to sham-injured animals after TBI.76,77,90,91”
From Effects of Traumatic Brain Injury on the Orexin/Hypocretin System (2025) · cites this paper as [91]
Cites
Traumatic brain injury: integrated approaches to improve prevention, clinical care, and research
Maas, A. I. R., Menon, D. K., Adelson, P. D., Andelic, N., Bell, M. J., Belli, A., Bragge, P., Brazinova, A., Büki, A., Chesnut, R. M., et al. (2017) · The Lancet Neurology · doi:10.1016/s1474-4422(17)30371-x · Cited by 2,609 · see citing works
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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
- Dong, X., Ye, W., Tang, Y., Wang, J., Zhong, L., Xiong, J., Liu, H., Lu, G., & Feng, Z.
- Affiliations
- First Affiliated Hospital of Nanchang University (CN)
- Corresponding author
- Feng, Zhen
- Venue
- World Neurosurgery
- Publisher
- Elsevier BV
- Published
- 2021-08
- Volume
- 152
- Pages
- e321-e331
- ISSN
- 1878-8750 (ISSN-L)
- OpenAlex
- W3164925994
- Cited by
- 18
- References
- 1
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 4 · 2023: 4 · 2022: 4
- FWCI
- 1.43
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- World Neurosurgery (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81260295, 81660382)
- Topics
- Health Sciences › Medicine › Neurology › Neurological disorders and treatments
- Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
- Keywords
- deep brain stimulation, lateral hypothalamus, traumatic brain injury, coma, wakefulness, SB-334867, alpha1-adrenoceptor subtypes, GABAB receptors, prefrontal cortex, consciousness recovery, EEG, delta oscillations, rats, adrenergic signaling
- MeSH terms
- Orexins, Brain Injuries, Traumatic, Anesthesia, Animals, Benzoxazoles, Coma, Consciousness, Delta Rhythm, Electroencephalography, Female, Hypothalamic Area, Lateral, Injections, Intraventricular, Functional Laterality, Male, Naphthyridines, Urea, Wakefulness, Signal Transduction, Rats, Sprague-Dawley, Receptors, GABA, Receptors, Adrenergic, alpha-1, Deep Brain Stimulation, Rats, Orexin Receptors
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