An Effective Method for Acute Vagus Nerve Stimulation in Experimental Inflammation

Caravaca, April S.; Gallina, Alessandro L; Tarnawski, Laura; Tracey, Kevin J.; Pavlov, Valentin A.; Levine, Yaakov A.; Olofsson, Peder S.

doi:10.3389/fnins.2019.00877

Cited by 49 publications

(45 citation statements)

References 39 publications

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“…Alternatively, those 2 animals could simply be non-responders seen often in acute studies [38,40]. Our data also suggest that the presence of a heart rate response in an implant does not necessarily predict engagement of the anti-inflammatory pathway, which is consistent with previous findings in acute studies [40,84].…”

Section: Discussionsupporting

confidence: 88%

“…The potential wide therapeutic applicability of VNS lies in part in its ability to modulate inflammation, a process thought to underlie the pathogenesis of many common diseases [23][24][25][26]. This effect was first described in a model of LPS endotoxemia, wherein acute VNS suppressed TNF release [19], and has since been established as a functional read-out of the anti-inflammatory action of VNS [38].…”

Section: Discussionmentioning

confidence: 99%

“…Experimental testing of VNS as therapy for chronic diseases requires a long-term VN implant and, as of yet, has been mostly limited to neurological and cardiovascular diseases modeled in rats and large animals [11,13,15,[27][28][29][30][31][32][33][34]. Even though the mouse is the species of choice in the study of disease mechanisms and is considered the standard for pre-clinical therapeutic screening [35,36], translational VNS research in mice has been limited to acute delivery of stimulation [37][38][39][40][41][42][43][44][45]. This is mainly due to the significant surgical and technical challenges associated with a mechanically- [46][47][48] and electrochemically- [49,50] stable long-term interface with the microscopic anatomy of the mouse vagus nerve.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

An implant for long-term cervical vagus nerve stimulation in mice

Mughrabi

Hickman

Jayaprakash

et al. 2020

Preprint

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Vagus nerve stimulation (VNS) is a neuromodulation therapy with the potential to treat a wide range of chronic conditions in which inflammation is implicated, including type 2 diabetes, obesity and atherosclerosis. Many of these diseases have well-established mouse models, but due to the significant surgical and engineering challenges that accompany a reliable interface for long-term VNS in mice, the therapeutic implications of this bioelectronic therapy remain unexplored. Here, we describe a long-term VNS implant in mice, developed at 3 research laboratories and validated for across-lab reproducibility. Implant functionality was evaluated over 3-8 weeks in 81 anesthetized or behaving mice by determining the stimulus intensity required to elicit a change in heart rate (heart rate threshold, HRT). HRT was also used as a method to standardize stimulation dosing. Overall, 60-90% of implants produced stimulusevoked physiological responses for at least 4 weeks, with HRT values stabilizing after the second week of implantation. Furthermore, stimulation delivered through 6-week-old implants decreased TNF levels in a subset of mice with acute inflammation caused by endotoxemia. Histological examination of 4-to 6-weekold implants revealed fibrotic encapsulation and no gross fiber loss. This implantation and dosing approach provides a tool to systematically investigate the therapeutic potential of long-term VNS in chronic diseases modeled in the mouse, the most widely used vertebrate species in biomedical research.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

An implant for long-term cervical vagus nerve stimulation in mice

Mughrabi

Hickman

Jayaprakash

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…In the clinical setting, electrical neural prostheses can modulate, restore, or bypass nerves, with the aim to restore sensory,5 motor, or autonomic functions of the diseased or damaged nervous system 4,6. There are several neuronal prostheses used on a large scale, such as cochlear implants, deep brain stimulators, and a variety of peripheral nerve stimulators for treating inflammatory disorders and chronic pain 7. At present, the scope of new applications of bioelectronic medicine is expanding at a rapid pace 8.…”

Section: Introductionmentioning

confidence: 99%

Extracellular Photovoltage Clamp Using Conducting Polymer‐Modified Organic Photocapacitors

Ejneby

Migliaccio

Gicevičius

et al. 2020

Adv Materials Technologies

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Optoelectronic control of physiological processes accounts for new possibilities ranging from fundamental research to treatment of disease. Among nongenetic light‐driven approaches, organic semiconductor‐based device platforms such as the organic electrolytic photocapacitor (OEPC) offer the possibility of localized and wireless stimulation with a minimal mechanical footprint. Optimization of efficiency hinges on increasing effective capacitive charge delivery. Herein, a simple strategy to significantly enhance the photostimulation performance of OEPC devices by employing coatings of the conducting polymer formulation poly(3,4‐ethylenedioxythiophene):poly(styrene sulfonate), or PEDOT:PSS is reported. This modification increases the charge density of the stimulating photoelectrodes by a factor of 2–3 and simultaneously decreases the interfacial impedance. The electrophysiological effects of PEDOT:PSS‐derivatized OEPCs on Xenopus laevis oocyte cells on membrane potential are measured and voltage‐clamp techniques are used, finding an at‐least twofold increase in capacitive coupling. The large electrolytic capacitance of PEDOT:PSS allows the OEPC to locally alter the extracellular voltage and keep it constant for long periods of time, effectively enabling a unique type of light‐controlled membrane depolarization for measurements of ion channel opening. The finding that PEDOT:PSS‐coated OEPCs can remain stable after a 50‐day accelerated ageing test demonstrates that PEDOT:PSS modification can be applied for fabricating reliable and efficient optoelectronic stimulation devices.

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“…Vagus nerve stimulation (VNS) exerts anti-inflammatory effects in a variety of diseases 18 and is considered a safe and effective therapy for refractory depression, schizophrenia, somatoform disorder, refractory epilepsy, and inflammatory bowel disease. [19][20][21][22][23] Our previous study also revealed that VNS improved consciousness recovery from TBI.…”

Section: Introductionmentioning

confidence: 99%

Vagus Nerve Stimulation Attenuates Early Traumatic Brain Injury by Regulating the NF-κB/NLRP3 Signaling Pathway

Tang

Dong

Chen

et al. 2020

Neurorehabil Neural Repair

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Background Traumatic brain injury (TBI) is a major cause of death and disability worldwide. Oxidative stress, inflammation, and apoptosis are vital pathophysiological features post-TBI. Objectives Research has shown that vagus nerve stimulation (VNS) can attenuate oxidative stress in various diseases. However, the critical role of VNS in TBI is still not completely understood. This study investigated the protective effects and potential mechanism of VNS on TBI. Methods Male Sprague-Dawley rats were randomized into 3 groups: sham, TBI, and TBI + VNS. The TBI model was induced in rats by the free-fall drop method. The vagal nerve trunk was separated, and VNS was performed after establishing the TBI model. Results The results showed that VNS significantly ameliorated tissue damage, neurological deficits, and cerebral edema, compared with the sham VNS group. Additionally, VNS alleviated oxidative stress, inflammation, and apoptosis in the pericontusive cortex of rats after TBI. VNS also significantly suppressed expression of the nuclear factor-κB (NF-κB) protein in the nucleus and activation of the nucleotide-binding domain–like receptor protein 3 (NLRP3) inflammasome. Conclusions Taken together, the present study indicates that VNS may attenuate brain damage after TBI by inhibiting oxidative stress, inflammation, and apoptosis, possibly through the NF-κB/NLRP3 signaling pathway.

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An Effective Method for Acute Vagus Nerve Stimulation in Experimental Inflammation

Cited by 49 publications

References 39 publications

An implant for long-term cervical vagus nerve stimulation in mice

An implant for long-term cervical vagus nerve stimulation in mice

Extracellular Photovoltage Clamp Using Conducting Polymer‐Modified Organic Photocapacitors

Vagus Nerve Stimulation Attenuates Early Traumatic Brain Injury by Regulating the NF-κB/NLRP3 Signaling Pathway

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