Vagus Nerve Stimulation Improves Cognitive Impairment After Traumatic Brain Injury Through the "Microbiota-Gut Immune Barrier-Neuroinflammation" Axis | [Pakistan Veterinary Journal • 2025]

Author(s):

1. Yue Zhao: Department of Rehabilitation, The 1st affiliated hospital, Jiangxi Medical College, Nanchang University,Nanchang,China

2. Xing Li: Jiangxi Provincial People's Hospital, The 1st affiliated Hospital of Nanchang Medical College, China

3. Lu Zhou: Department of Rehabilitation, The 1st affiliated hospital, Jiangxi Medical College, Nanchang University,Nanchang,China

4. Xiuxiu Xu: Department of Rehabilitation, The 1st affiliated hospital, Jiangxi Medical College, Nanchang University,Nanchang,China

5. Kangkang Ren: Jiangxi Provincial People's Hospital, The 1st affiliated Hospital of Nanchang Medical College, China

6. Duoduo Ren: College of Veterinary Medicine, Northwest A&F University, China

7. Lijuan Quan: Department of Rehabilitation, The 1st affiliated hospital, Jiangxi Medical College, Nanchang University,Nanchang,China

Abstract:

Traumatic brain injury (TBI) often leads to physical and mental dysfunction in human and companion animal. Studies have shown that the gut microbiota influences TBI progression and prognosis through the gut-brain axis. Vagus nerve stimulation (VNS) has neuroprotective and cognitive benefits, but its mechanism for alleviating cognitive impairment after TBI remains unclear. A TBI model was established using a controlled cortical impact device (CCI), with 3-day VNS intervention. To investigate the relationship between VNS improving cognitive impairment after TBI and remodeling gut dysbiosis, antibiotics were used to clear the gut microbiota of TBI mice. Cognitive improvement was evaluated via behavioral tests. Inflammation, gut microbiota, and colonic damage were analyzed via Nissl staining, immunofluorescence, Hematoxylin-eosin staining, ELISA, 16S rRNA gene sequencing, qRT-PCR, and western blot. Our study revealed that VNS markedly enhanced cognition and inhibits neuroinflammation in TBI mice by modulating the TLR4/MyD88/NF-?B pathway, while simultaneously reducing the abundance of cognition-impairing associated Escherichia_Shigella and ameliorating intestinal barrier dysfunction. After antibiotics eliminated the microbe, the effects of VNS on improving cognition, alleviating colon injury, and suppressing neuroinflammation were weakened. These findings reveal a novel microbiota-gut immune barrier-neuroinflammation axis, supporting VNS-based interventions for TBI management in both humans and companion animals.

Page(s): 1073-1084

DOI: 10.29261/pakvetj/2025.252

Published: Journal: Pakistan Veterinary Journal, Volume: 45, Issue: 3, Year: 2025

Keywords:

Traumatic brain injury , microbiota , Neuroinflammation , Cognitive impairment , Vagus Nerve Stimulation , Gut immune barrier , Human and companion animals

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