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Vagus Nerve Stimulation Prevents Endothelial Necroptosis to Alleviate Blood-Spinal Cord Barrier Disruption After Spinal Cord Injury.
Chen, Hui; Feng, Zhou; Min, Lingxia; Tan, Mingliang; Zhang, Dongyun; Gong, Qiuwen; Liu, Hongliang; Hou, Jingming.
Afiliación
  • Chen H; Department of Rehabilitation, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.
  • Feng Z; Department of Rehabilitation, Wusheng Hospital of Traditional Chinese Medicine, Sichuan, China.
  • Min L; Department of Rehabilitation, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.
  • Tan M; Department of Rehabilitation, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.
  • Zhang D; Department of Rehabilitation, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.
  • Gong Q; Department of Rehabilitation, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.
  • Liu H; Department of Rehabilitation, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.
  • Hou J; Department of Rehabilitation, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.
Mol Neurobiol ; 60(11): 6466-6475, 2023 Nov.
Article en En | MEDLINE | ID: mdl-37460917
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Traumatismos de la Médula Espinal / Estimulación del Nervio Vago Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Mol Neurobiol Asunto de la revista: BIOLOGIA MOLECULAR / NEUROLOGIA Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Traumatismos de la Médula Espinal / Estimulación del Nervio Vago Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Mol Neurobiol Asunto de la revista: BIOLOGIA MOLECULAR / NEUROLOGIA Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos