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Anatomical and clinical implications of vagal modulation of the spleen.

ABSTRACT: The vagus nerve coordinates most physiologic functions including the cardiovascular and immune systems. This mechanism has significant clinical implications because electrical stimulation of the vagus nerve can control inflammation and organ injury in infectious and inflammatory disorders. The complex mechanisms that mediate vagal modulation of systemic inflammation are mainly regulated via the spleen. More specifically, vagal stimulation prevents organ injury and systemic inflammation by inhibiting the production of cytokines in the spleen. However, the neuronal regulation of the spleen is controversial suggesting that it can be mediated by either monosynaptic innervation of the splenic parenchyma or secondary neurons from the celiac ganglion depending on the experimental conditions. Recent physiologic and anatomic studies suggest that inflammation is regulated by neuro-immune multi-synaptic interactions between the vagus and the splanchnic nerves to modulate the spleen. Here, we review the current knowledge on these interactions, and discuss their experimental and clinical implications in infectious and inflammatory disorders.

SUBMITTER: Bassi GS

PROVIDER: S-EPMC7211143 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Anatomical and clinical implications of vagal modulation of the spleen.

Bassi Gabriel S GS Kanashiro Alexandre A Coimbra Norberto C NC Terrando Niccolò N Maixner William W Ulloa Luis L

Neuroscience and biobehavioral reviews 20200222

The vagus nerve coordinates most physiologic functions including the cardiovascular and immune systems. This mechanism has significant clinical implications because electrical stimulation of the vagus nerve can control inflammation and organ injury in infectious and inflammatory disorders. The complex mechanisms that mediate vagal modulation of systemic inflammation are mainly regulated via the spleen. More specifically, vagal stimulation prevents organ injury and systemic inflammation by inhibi ...[more]

PMID: 32061636

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Project description:Vagal fibers travel inside fascicles and form branches to innervate organs and regulate organ functions. Existing vagus nerve stimulation (VNS) therapies activate vagal fibers non-selectively, often resulting in reduced efficacy and side effects from non-targeted organs. The transverse and longitudinal arrangement of fibers inside the vagal trunk with respect to the functions they mediate and organs they innervate is unknown, however it is crucial for selective VNS. Using micro-computed tomography imaging, we tracked fascicular trajectories and found that, in swine, sensory and motor fascicles are spatially separated cephalad, close to the nodose ganglion, and merge caudad, towards the lower cervical and upper thoracic region; larynx-, heart- and lung-specific fascicles are separated caudad and progressively merge cephalad. Using quantified immunohistochemistry at single fiber level, we identified and characterized all vagal fibers and found that fibers of different morphological types are differentially distributed in fascicles: myelinated afferents and efferents occupy separate fascicles, myelinated and unmyelinated efferents also occupy separate fascicles, and small unmyelinated afferents are widely distributed within most fascicles. We developed a multi-contact cuff electrode to accommodate the fascicular structure of the vagal trunk and used it to deliver fascicle-selective cervical VNS in anesthetized and awake swine. Compound action potentials from distinct fiber types, and physiological responses from different organs, including laryngeal muscle, cough, breathing, and heart rate responses are elicited in a radially asymmetric manner, with consistent angular separations that agree with the documented fascicular organization. These results indicate that fibers in the trunk of the vagus nerve are anatomically organized according to functions they mediate and organs they innervate and can be asymmetrically activated by fascicular cervical VNS.

Dataset Information

Anatomical and clinical implications of vagal modulation of the spleen.

Publications

Anatomical and clinical implications of vagal modulation of the spleen.

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