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Cited by 23Traumatic Brain Injury and Neurovascular DisturbancesUltrasound and Hyperthermia ApplicationsTraumatic Brain Injury Research

Low-intensity focused ultrasound attenuates early traumatic brain injury by OX-A/NF-κB/NLRP3 signaling pathway

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Huang, Lianghua, Kang, Junwei, Chen, Gengfa, Ye, Wen, Meng, Xiangqiang, Du, Qing, Feng, Zhen·2022·Aging
DOI 10.18632/aging.204290PMC PMC9550253
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Abstract

BACKGROUND: Traumatic brain injury (TBI) is a serious hazard to human health and is characterized by high rates of disability and mortality. It is necessary to explore new effective treatment methods to reduce the impact of TBI on individuals and society. As an emerging neuromodulation technique, ultrasound is used to treat some neurological diseases, but the neuroprotective mechanism of low-intensity focused ultrasound (LIFUS) in TBI remains unclear. We aimed to investigate the protective effects and potential mechanisms of LIFUS in TBI. METHODS: A rat model of TBI was established using the free-fall method. After establishing the TBI model, the hypothalamus region was covered with LIFUS radiation, and an orexin receptor 1 (OXR1) antagonist (SB334867) was injected intraperitoneally. Neurobehavioral examination, Nissl staining, hematoxylin and eosin staining of the brain tissue, and brain water content, were performed 3 days later. Western blotting, quantitative real-time polymerase chain reaction, immunofluorescence staining, and immunohistochemical staining, were used to evaluate the neuroprotective mechanisms of LIFUS. RESULTS: LIFUS improved tissue damage, neurological deficits, and brain edema. LIFUS can increase the expression of orexin-A (OX-A) and OXR1, significantly inhibit the activation of nuclear factor-κB (NF-κB) protein and nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome after TBI, and reduce the release of pro-inflammatory factors after TBI; however, SB334867 can reverse this effect. CONCLUSIONS: This study suggests that LIFUS may play a neuroprotective role by promoting the release of OX-A from the hypothalamus and inhibiting the inflammatory response after TBI through the OX-A /NF-κB/NLRP3 pathway.

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  • In one study, there is both an increase in neuropeptide after injury and a decrease in orexin receptor levels, meaning the two may not correspond with one another.

    “In this particular study, there is both an increase in neuropeptide after injury and a decrease in orexin receptor levels, meaning that the two may not correspond with one another.”

    From Effects of Traumatic Brain Injury on the Orexin/Hypocretin System (2025) · cites this paper as [78]

    The Results section (“LIFUS increased the expression of OX-A and OXR1”; page unavailable) reports the opposite directions after injury: neuropeptide OX-A was lower in the TBI group than in the sham group, while orexin receptor 1 (OXR1) was higher. The Discussion also says OX-A decreased and OXR1 increased after TBI. Although the two levels moved in different directions, the claim reverses both changes. (LLM, conf=0.94)

    Checked by a reasoning model — may be wrong.

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  • 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 [78]

  • One study reports increased orexin receptor levels compared to sham-injured animals 3 days post-injury.

    “in one study,78 reports increased orexin receptor levels compared to sham-injured animals 3 days post-injury.”

    From Effects of Traumatic Brain Injury on the Orexin/Hypocretin System (2025) · cites this paper as [78]

  • Several other studies, including the authors' own, found a decrease in orexin after TBI.

    “In several other studies, including ours, there was a decrease in orexin after TBI.49,77,78”

    From Effects of Traumatic Brain Injury on the Orexin/Hypocretin System (2025) · cites this paper as [78]

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Cited by

Sorted by citations

Authors
Huang, L., Kang, J., Chen, G., Ye, W., Meng, X., Du, Q., & Feng, Z.
Affiliations
First Affiliated Hospital of Nanchang University (CN)
Corresponding author
Feng, Zhen
ORCID
Venue
Aging
Publisher
Impact Journals, LLC
Published
2022-09-16
Volume
14
Issue
18
Pages
7455-7469
ISSN
1945-4589 (ISSN-L)
DOI
10.18632/aging.204290
PMC
PMC9550253
OpenAlex
W4296274435
Cited by
23
References
0
Citations by year
2026: 3 · 2025: 9 · 2024: 8 · 2023: 3
FWCI
2.63
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Aging (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
National Natural Science Foundation of China (82160437)
Topics
  • Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
  • Physical Sciences › Engineering › Biomedical Engineering › Ultrasound and Hyperthermia Applications
  • Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
Keywords
low-intensity focused ultrasound, traumatic brain injury, neuroprotection, orexin-A, orexin-1 receptor, NF-κB, NLRP3 inflammasome, hypothalamus, neuroinflammation, cerebral edema, SB-334867, neuromodulation
MeSH terms
Orexins, Brain Injuries, Traumatic, NLR Family, Pyrin Domain-Containing 3 Protein, Animals, Eosine Yellowish-(YS), Hematoxylin, Humans, Nucleotides, Water, Signal Transduction, NF-kappa B, Rats, Sprague-Dawley, Rats, Inflammasomes, Orexin Receptors

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