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Vagus nerve stimulation activates two distinct neuroimmune circuits converging in the spleen to protect mice from kidney injury.

Citation
Tanaka, S., et al. “Vagus Nerve Stimulation Activates Two Distinct Neuroimmune Circuits Converging In The Spleen To Protect Mice From Kidney Injury.”. Proceedings Of The National Academy Of Sciences Of The United States Of America.
Center Vanderbilt University
Author Shinji Tanaka, Chikara Abe, Stephen B G Abbott, Shuqiu Zheng, Yusuke Yamaoka, Jonathan E Lipsey, Nataliya I Skrypnyk, Junlan Yao, Tsuyoshi Inoue, William T Nash, Daniel S Stornetta, Diane L Rosin, Ruth L Stornetta, Patrice G Guyenet, Mark D Okusa
Keywords acute kidney injury, neuroimmune interactions, Sympathetic nervous system, vagus nerve stimulation
Abstract

Acute kidney injury is highly prevalent and associated with high morbidity and mortality, and there are no approved drugs for its prevention and treatment. Vagus nerve stimulation (VNS) alleviates inflammatory diseases including kidney disease; however, neural circuits involved in VNS-induced tissue protection remain poorly understood. The vagus nerve, a heterogeneous group of neural fibers, innervates numerous organs. VNS broadly stimulates these fibers without specificity. We used optogenetics to selectively stimulate vagus efferent or afferent fibers. Anterograde efferent fiber stimulation or anterograde (centripetal) sensory afferent fiber stimulation both conferred kidney protection from ischemia-reperfusion injury. We identified the C1 neurons-sympathetic nervous system-splenic nerve-spleen-kidney axis as the downstream pathway of vagus afferent fiber stimulation. Our study provides a map of the neural circuits important for kidney protection induced by VNS, which is critical for the safe and effective clinical application of VNS for protection from acute kidney injury.

Year of Publication
2021
Journal
Proceedings of the National Academy of Sciences of the United States of America
Volume
118
Issue
12
Date Published
03/2021
ISSN Number
1091-6490
DOI
10.1073/pnas.2021758118
Alternate Journal
Proc Natl Acad Sci U S A
PMID
33737395
PMCID
PMC7999957
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