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Cited by 5Traumatic Brain Injury and Neurovascular DisturbancesTraumatic Brain Injury ResearchTranscranial Magnetic Stimulation Studies

Trigeminal nerve electrical stimulation attenuates early traumatic brain injury through the TLR4/NF-κB/NLRP3 signaling pathway mediated by orexin-A/OX1R system

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Kang, Junwei, Zhou, Yifan, Xiong, Qi, Dong, Xiaoyang·2024·Aging
DOI 10.18632/aging.205795PMC PMC11131994
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Abstract

BACKGROUND: Traumatic brain injury (TBI) is a significant contributor to global mortality and disability, and emerging evidence indicates that trigeminal nerve electrical stimulation (TNS) is a promising therapeutic intervention for neurological impairment following TBI. However, the precise mechanisms underlying the neuroprotective effects of TNS in TBI are poorly understood. Thus, the objective of this study was to investigate the potential involvement of the orexin-A (OX-A)/orexin receptor 1 (OX1R) mediated TLR4/NF-κB/NLRP3 signaling pathway in the neuroprotective effects of TNS in rats with TBI. METHODS: Sprague-Dawley rats were randomly assigned to four groups: sham, TBI, TBI+TNS+SB334867, and TBI+TNS. TBI was induced using a modified Feeney's method, and subsequent behavioral assessments were conducted to evaluate neurological function. The trigeminal nerve trunk was isolated, and TNS was administered following the establishment of the TBI model. The levels of neuroinflammation, brain tissue damage, and proteins associated with the OX1R/TLR4/NF-κB/NLRP3 signaling pathway were assessed using hematoxylin-eosin staining, Nissl staining, western blot analysis, quantitative real-time polymerase chain reaction, and immunofluorescence techniques. RESULTS: The findings of our study indicate that TNS effectively mitigated tissue damage, reduced brain edema, and alleviated neurological deficits in rats with TBI. Furthermore, TNS demonstrated the ability to attenuate neuroinflammation levels and inhibit the expression of proteins associated with the TLR4/NF-κB/NLRP3 signaling pathway. However, it is important to note that the aforementioned effects of TNS were reversible upon intracerebroventricular injection of an OX1R antagonist. CONCLUSION: TNS may prevent brain damage and relieve neurological deficits after a TBI by inhibiting inflammation, possibly via the TLR4/NF-κB/NLRP3 signaling pathway mediated by OX-A/OX1R.

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  • 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 [90]

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Cited by

Sorted by citations

Authors
Kang, J., Zhou, Y., Xiong, Q., & Dong, X.
Affiliations
Nanchang University (CN)
Corresponding author
Dong, Xiaoyang
ORCID
Venue
Aging
Publisher
Impact Journals, LLC
Published
2024-05-06
Volume
16
Issue
9
Pages
7946-7960
ISSN
1945-4589 (ISSN-L)
DOI
10.18632/aging.205795
PMC
PMC11131994
OpenAlex
W4396673433
Cited by
5
References
1
Citations by year
2026: 1 · 2025: 4
FWCI
1.34
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 (20224BAB216042, 82,260,457)
  • Natural Science Foundation of Jiangxi Province (20224BAB216042)
Topics
  • Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
  • Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
  • Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
Keywords
traumatic brain injury, orexin-A, OX1 receptor, neuroinflammation, neuroprotection, cerebral edema, neurological deficit, SB-334867
MeSH terms
Orexins, Brain Injuries, Traumatic, NLR Family, Pyrin Domain-Containing 3 Protein, Animals, Disease Models, Animal, Electric Stimulation Therapy, Male, Trigeminal Nerve, Signal Transduction, NF-kappa B, Rats, Sprague-Dawley, Toll-Like Receptor 4, Rats, Orexin Receptors

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