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Cited by 12Traumatic Brain Injury and Neurovascular DisturbancesTranscranial Magnetic Stimulation StudiesTraumatic Brain Injury Research

Transcranial direct current stimulation promotes angiogenesis and improves neurological function via the OXA-TF-AKT/ERK signaling pathway in traumatic brain injury

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Ren, Bingkai, Kang, Junwei, Wang, Yan, Meng, Xiangqiang, Huang, Ying, Bai, Yang, Feng, Zhen·2024·Aging
DOI 10.18632/aging.205724PMC PMC11042948
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Abstract

Traumatic brain injury (TBI) and its resulting complications pose a major challenge to global public health, resulting in increased rates of disability and mortality. Cerebrovascular dysfunction is nearly universal in TBI cases and is closely associated with secondary injury after TBI. Transcranial direct current stimulation (tDCS) shows great potential in the treatment of TBI; however, the exact mechanism remains elusive. In this study, we performed in vivo and in vitro experiments to explore the effects and mechanisms of tDCS in a controlled cortical impact (CCI) rat model simulating TBI. In vivo experiments show that tDCS can effectively reduce brain tissue damage, cerebral edema and neurological deficits. The potential mechanism may be that tDCS improves the neurological function of rats by increasing orexin A (OXA) secretion, upregulating the TF-AKT/ERK signaling pathway, and promoting angiogenesis at the injury site. Cellular experiments showed that OXA promoted HUVEC migration and angiogenesis, and these effects were counteracted by the ERK1/2 inhibitor LY3214996. The results of Matrigel experiment in vivo showed that TNF-a significantly reduced the ability of HUVEC to form blood vessels, but OXA could rescue the effect of TNF-a on the ability of HUVEC to form blood vessels. However, LY3214996 could inhibit the therapeutic effect of OXA. In summary, our preliminary study demonstrates that tDCS can induce angiogenesis through the OXA-TF-AKT/ERK signaling pathway, thereby improving neurological function in rats with TBI.

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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 [77]

    The Results section (“tDCS promotes the expression of OXA and OX1R in TBI rats”; page unavailable) reports the opposite comparison: OX1R receptor expression was significantly lower in TBI rats than in sham rats. OX1R expression increased after tDCS treatment, not after TBI alone. (LLM, conf=0.92)

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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 [77]

  • 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 [77]

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Cited by

Sorted by citations

Authors
Ren, B., Kang, J., Wang, Y., Meng, X., Huang, Y., Bai, Y., & Feng, Z.
Affiliations
Nanchang University (CN)
Corresponding author
Feng, Zhen
ORCID
Venue
Aging
Publisher
Impact Journals, LLC
Published
2024-04-05
Volume
16
Issue
7
Pages
6566-6587
ISSN
1945-4589 (ISSN-L)
DOI
10.18632/aging.205724
PMC
PMC11042948
OpenAlex
W4393998229
Cited by
12
References
2
Citations by year
2026: 1 · 2025: 10 · 2024: 1
FWCI
3.21
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
  • Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
  • Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
Keywords
transcranial direct current stimulation, traumatic brain injury, angiogenesis, orexin-A, ERK1/2, cerebral edema, neurological function, TNF-α, LY3214996, secondary brain injury
MeSH terms
Orexins, Brain Injuries, Traumatic, Angiogenesis, Animals, Disease Models, Animal, Humans, Male, Signal Transduction, Rats, Sprague-Dawley, Neovascularization, Physiologic, MAP Kinase Signaling System, Proto-Oncogene Proteins c-akt, Rats, Human Umbilical Vein Endothelial Cells, Transcranial Direct Current Stimulation

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