A review of vagus nerve stimulation as a therapeutic intervention.
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ABSTRACT:
SUBMITTER: Johnson RL
PROVIDER: S-EPMC5961632 | biostudies-other | 2018
REPOSITORIES: biostudies-other
Publications
A review of vagus nerve stimulation as a therapeutic intervention.
Johnson Rhaya L RL Wilson Christopher G CG
Journal of inflammation research 20180516
In this review, we provide an overview of the US Food and Drug Administration (FDA)-approved clinical uses of vagus nerve stimulation (VNS) as well as information about the ongoing studies and preclinical research to expand the use of VNS to additional applications. VNS is currently FDA approved for therapeutic use in patients aged >12 years with drug-resistant epilepsy and depression. Recent studies of VNS in in vivo systems have shown that it has anti-inflammatory properties which has led to m ...[more]
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Project description:INTRODUCTION:Lafora body disease (LBD) is a rare autosomal recessive disorder characterized by progression to inexorable dementia and frequent occipital seizures, in addition to myoclonus and generalized tonic-clonic seizures (GTCSs). It belongs to the group of progressive myoclonus epilepsies (PMEs), rare inherited neurodegenerative diseases with great clinical and genetic differences, as well as poor prognosis. Since those patients have a pharmacoresistant disease, an adjunctive treatment option is vagus nerve stimulation (VNS). To date, there are four reported cases of the utility of VNS in PME - in Unverricht-Lundborg disease (ULD), myoclonic epilepsy with ragged-red fibers (MERRF), Gaucher's disease, and in one case that remained unclassified. CASE PRESENTATION:A 19-year-old male patient had progressive myoclonus, GTCSs that often progressed to status epilepticus (SE), progressive cerebellar and extrapyramidal symptomatology, and dementia, and his disease was pharmacoresistant. We confirmed the diagnosis of LBD by genetic testing. After VNS implantation, in the one-year follow-up period, there was a complete reduction of GTCS and SE, significant regression of myoclonus, and moderate regression of cerebellar symptomatology. CONCLUSION:To our knowledge, this is the first reported case of the utility of VNS in LBD. Vagus nerve stimulation therapy may be considered a treatment option for different clinical entities of PME. Further studies with a larger number of patients are needed.
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Project description:Vagus nerve stimulation (VNS) is a bioelectronic therapy for disorders of the brain and peripheral organs, and a tool to study the physiology of autonomic circuits. Selective activation of afferent or efferent vagal fibers can maximize efficacy and minimize off-target effects of VNS. Anodal block (ABL) has been used to achieve directional fiber activation in nerve stimulation. However, evidence for directional VNS with ABL has been scarce and inconsistent, and it is unknown whether ABL permits directional fiber activation with respect to functional effects of VNS. Through a series of vagotomies, we established physiological markers for afferent and efferent fiber activation by VNS: stimulus-elicited change in breathing rate (?BR) and heart rate (?HR), respectively. Bipolar VNS trains of both polarities elicited mixed ?HR and ?BR responses. Cathode cephalad polarity caused an afferent pattern of responses (relatively stronger ?BR) whereas cathode caudad caused an efferent pattern (stronger ?HR). Additionally, left VNS elicited a greater afferent and right VNS a greater efferent response. By analyzing stimulus-evoked compound nerve potentials, we confirmed that such polarity differences in functional responses to VNS can be explained by ABL of A- and B-fiber activation. We conclude that ABL is a mechanism that can be leveraged for directional VNS.
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Project description:BackgroundVagus nerve stimulation (VNS) is effective in reducing inflammation in various diseases, such as rheumatoid arthritis, colitis and acute kidney injury. The anti-inflammatory effect of vagus nerve in these diseases necessitates the interactions of neural activation and α7 nicotinic acetylcholine receptors (α7nAChRs) on splenic macrophages. In this study, we aimed to investigate the effect of VNS on severity in experimental acute pancreatitis (AP).MethodsTwo independent AP models were used, which induced in ICR mice with caerulein or pancreatic duct ligation (PDL). Thirty minutes after modeling, the left cervical carotid sheath containing the vagus nerve was electrically stimulated for 2 min. Plasma lipase and amylase activities, TNF-α levels and pancreas histologic damage were evaluated. In caerulein mice, the percentages of α7nAChR+ macrophage in pancreas and spleen were assessed by flow cytometry. Furthermore, splenectomy and adoptive transfer of VNS-conditioned α7nAChR splenocytes were performed in caerulein mice to evaluate the role of spleen in the protective effect of VNS.ResultsVNS reduced plasma lipase and amylase activities, blunted the concentrations of TNF-α and protected against pancreas histologic damage in two AP models. Survival rates were improved in the PDL model after VNS. In caerulein AP mice, VNS increased the percentages of α7nAChR+ macrophages in pancreas and spleen. Adoptive transfer of VNS-treated α7nAChR splenocytes provided protection against pancreatitis in recipient mice. However, splenectomy did not abolish the protective effect of VNS.ConclusionsVNS reduces disease severity and attenuates inflammation in AP mice. This effect is independent of spleen and is probably related to α7nAChR on macrophage.
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