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Cited by 52Spinal Cord Injury ResearchNerve injury and regenerationTraumatic Brain Injury and Neurovascular Disturbances

Apolipoprotein E deficiency exacerbates spinal cord injury in mice: inflammatory response and oxidative stress mediated by NF-κB signaling pathway

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Yang, Xuan, Chen, Shurui, Shao, Zhenya, Li, Yuanlong, Wu, He, Li, Xian, Mao, Liang, Zhou, Zipeng +3 more·2018·Frontiers in Cellular Neuroscience
DOI 10.3389/fncel.2018.00142PMC PMC5974465
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Abstract

Spinal cord injury (SCI) is a severe neurological trauma that involves complex pathological processes. Inflammatory response and oxidative stress are prevalent during the second injury and can influence the functional recovery of SCI. Specially, Apolipoprotein E (APOE) induces neuronal repair and nerve regeneration, and the deficiency of Apoe impairs spinal cord-blood-barrier and reduces functional recovery after SCI. However, the mechanism by which Apoe mediates signaling pathways of inflammatory response and oxidative stress in SCI remains largely elusive. This study was designed to investigate the signaling pathways that regulate Apoe deficiency-dependent inflammatory response and oxidative stress in the acute stage of SCI. In the present study, Apoe-/- mice retarded functional recovery and had a larger lesion size when compared to wild-type mice after SCI. Moreover, deficiency of Apoe induced an exaggerated inflammatory response by increasing expression of IL-6 and IL-1β, and increased oxidative stress by reducing expression of Nrf2 and HO-1. Furthermore, lack of Apoe promoted neuronal apoptosis and decreased neuronal numbers in the anterior horn of the spinal cord after SCI. Mechanistically, we found that the absence of Apoe increased inflammation and oxidative stress through activation of NF-κB after SCI. In contrast, an inhibitor of nuclear factor-κB (NF-κB) (Pyrrolidine dithiocarbamate) alleviates these changes. Collectively, these results indicate that a critical role for activation of NF-κB in regulating Apoe-deficiency dependent inflammation and oxidative stress is detrimental to recovery after SCI.

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Cited by

Sorted by citations

Authors
Yang, X., Chen, S., Shao, Z., Li, Y., Wu, H., Li, X., Mao, L., Zhou, Z., Bai, L., Mei, X., & Liu, C.
Affiliations
  • Jinzhou Medical University (CN)
  • First Hospital of China Medical University (CN)
Corresponding author
  • Mei, Xifan
  • Liu, Chang
ORCID
Venue
Frontiers in Cellular Neuroscience
Publisher
Frontiers Media SA
Published
2018-05-23
Volume
12
Pages
142-142
ISSN
1662-5102 (ISSN-L)
DOI
10.3389/fncel.2018.00142
PMC
PMC5974465
OpenAlex
W2800347147
Cited by
52
References
8
Citations by year
2026: 8 · 2025: 5 · 2024: 6 · 2023: 5 · 2022: 5 · 2021: 10 · 2020: 3 · 2019: 8 · 2017: 1
FWCI
3.89
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Cellular Neuroscience (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
National Natural Science Foundation of China (31471138, 81671907, 81701898)
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Spinal Cord Injury Research
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
  • Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
Keywords
spinal cord injury, apolipoprotein E deficiency, NF-κB signaling, neuroinflammation, oxidative stress, Nrf2/HO-1 pathway, interleukin-6, IL-1β, neuronal apoptosis, pyrrolidine dithiocarbamate, functional recovery, lesion size, ApoE-deficient mice

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