Vagus Nerve Stimulation Prevents Endothelial Necroptosis to Alleviate Blood-Spinal Cord Barrier Disruption After Spinal Cord Injury.
Blood-spinal cord barrier
Endothelial cell
Necroptosis
Spinal cord injury
TNF-α
Vagus nerve stimulation
Journal
Molecular neurobiology
ISSN: 1559-1182
Titre abrégé: Mol Neurobiol
Pays: United States
ID NLM: 8900963
Informations de publication
Date de publication:
Nov 2023
Nov 2023
Historique:
received:
24
04
2023
accepted:
30
06
2023
medline:
28
9
2023
pubmed:
18
7
2023
entrez:
17
7
2023
Statut:
ppublish
Résumé
Vagus nerve stimulation (VNS) is a promising neuromodulation technique, which has been demonstrated to promote functional recovery after spinal cord injury (SCI) in our previous study. But the underlying mechanism remains to be explored. Using a compressed SCI model, our present study first demonstrated that activated microglia produce abundant tumor necrosis factor-α (TNF-α) to induce endothelial necroptosis via receptor-interacting protein kinase 1 (RIP1)/RIP3/mixed lineage kinase domain-like protein (MLKL) pathway, thus destroying the blood-spinal cord barrier (BSCB) after SCI. While both TNF-α specifical antibody (infliximab) and necroptosis inhibitor (necrostatin-1) alleviate BSCB disruption. Then our study found that VNS significantly inhibits microglia-derived TNF-α production and reduces expression of p-RIP3 and p-MLKL in endothelial cells. As expected, further results indicated that VNS mitigates the BSCB disruption, thus reducing inflammatory cells infiltration and neural damage. Finally, both electrophysiological evaluation and locomotor test demonstrated that VNS promotes motor function recovery after SCI. In conclusion, our data demonstrated VNS restricts microglia-derived TNF-α to prevent RIP1/RIP3/MLKL mediated endothelial necroptosis, thus alleviating the decisive pathophysiological BSCB disruption to reduce neuroinflammation and neural damage, which ultimately promotes motor function recovery after SCI. Therefore, these results further elaborate that VNS might be a promising therapeutic strategy for SCI. Vagus nerve stimulation prevents microglia-derived TNF-α induced endothelial necroptosis to alleviate blood-spinal cord barrier disruption after spinal cord injury.
Identifiants
pubmed: 37460917
doi: 10.1007/s12035-023-03477-7
pii: 10.1007/s12035-023-03477-7
doi:
Substances chimiques
Tumor Necrosis Factor-alpha
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
6466-6475Subventions
Organisme : National Natural Science Foundation of China
ID : 82172542
Organisme : National Natural Science Foundation of China
ID : U19A2082
Organisme : Chongqing Talents Project
ID : CQYC20210510203
Organisme : Natural Science Foundation of Chongqing
ID : cst2021jcyj-msxmX0612
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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