Auricular vagus nerve stimulation protects against postoperative cognitive dysfunction by attenuating neuroinflammation and neurodegeneration in aged rats

Cai, Liang; Lu, Kai; Chen, Xin; Huang, Jingyuan; Zhang, Baoping; Zhang, Han

doi:10.1016/j.neulet.2019.03.034

Cited by 28 publications

(18 citation statements)

References 26 publications

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“…Experimental animal studies confirmed the benefits of tVNS by using endotoxemic rodent models and shed light on underlying mechanisms [115,116]. Remarkably, taVNS also reduced cognitive dysfunction in a postoperative model of aged rats [117] and in a murine model of AD [118] via a decrease of neuroinflammation. In human clinics, however, taVNS has not been tested so far in AD [14,119].…”

Section: Non-invasive Vagus Nerve Stimulation As a Novel Therapeutic Approach For Covid-19?mentioning

confidence: 63%

The Vagal Autonomic Pathway of COVID-19 at the Crossroad of Alzheimer’s Disease and Aging: A Review of Knowledge

Rangon

Krantic

Moyse

et al. 2020

ADR

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Coronavirus Disease 2019 (COVID-19) pandemic-triggered mortality is significantly higher in older than in younger populations worldwide. Alzheimer’s disease (AD) is related to aging and was recently reported to be among the major risk factors for COVID-19 mortality in older people. The symptomatology of COVID-19 indicates that lethal outcomes of infection rely on neurogenic mechanisms. The present review compiles the available knowledge pointing to the convergence of COVID-19 complications with the mechanisms of autonomic dysfunctions in AD and aging. The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is prone to neuroinvasion from the lung along the vagus nerve up to the brainstem autonomic nervous centers involved in the coupling of cardiovascular and respiratory rhythms. The brainstem autonomic network allows SARS-CoV-2 to trigger a neurogenic switch to hypertension and hypoventilation, which may act in synergy with aging- and AD-induced dysautonomias, along with an inflammatory “storm”. The lethal outcomes of COVID-19, like in AD and unhealthy aging, likely rely on a critical hypoactivity of the efferent vagus nerve cholinergic pathway, which is involved in lowering cardiovascular pressure and systemic inflammation tone. We further discuss the emerging evidence supporting the use of 1) the non-invasive stimulation of vagus nerve as an additional therapeutic approach for severe COVID-19, and 2) the demonstrated vagal tone index, i.e., heart rate variability, via smartphone-based applications as a non-serological low-cost diagnostic of COVID-19. These two well-known medical approaches are already available and now deserve large-scale testing on human cohorts in the context of both AD and COVID-19.

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Section: Non-invasive Vagus Nerve Stimulation As a Novel Therapeutic Approach For Covid-19?mentioning

confidence: 63%

The Vagal Autonomic Pathway of COVID-19 at the Crossroad of Alzheimer’s Disease and Aging: A Review of Knowledge

Rangon

Krantic

Moyse

et al. 2020

ADR

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“…84 A similar effect on hippocampal inflammation has been demonstrated in a model of exploratory laparotomy in aged mice. 85 The positive impact of VNS in numerous cognitive studies in humans suggests that this approach may also have perioperative utility in reducing POCD.…”

Section: Discussionmentioning

confidence: 99%

The potential for autonomic neuromodulation to reduce perioperative complications and pain: a systematic review and meta-analysis

Patel

Weber

Gourine

et al. 2022

British Journal of Anaesthesia

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Background: Autonomic dysfunction promotes organ injury after major surgery through numerous pathological mechanisms. Vagal withdrawal is a key feature of autonomic dysfunction, and it may increase the severity of pain. We systematically evaluated studies that examined whether vagal neuromodulation can reduce perioperative complications and pain. Methods: Two independent reviewers searched PubMed, EMBASE, and the Cochrane Register of Controlled Clinical Trials for studies of vagal neuromodulation in humans. Risk of bias was assessed; I 2 index quantified heterogeneity. Primary outcomes were organ dysfunction (assessed by measures of cognition, cardiovascular function, and inflammation) and pain. Secondary outcomes were autonomic measures. Standardised mean difference (SMD) using the inverse variance random-effects model with 95% confidence interval (CI) summarised effect sizes for continuous outcomes. Results: From 1258 records, 166 full-text articles were retrieved, of which 31 studies involving patients (n¼721) or volunteers (n¼679) met the inclusion criteria. Six studies involved interventional cardiology or surgical patients. Indirect stimulation modalities (auricular [n¼23] or cervical transcutaneous [n¼5]) were most common. Vagal neuromodulation reduced pain (n¼10 studies; SMD¼2.29 [95% CI, 1.08e3.50]; P¼0.0002; I 2 ¼97%) and inflammation (n¼6 studies; SMD¼1.31 [0.45e2.18]; P¼0.003; I 2 ¼91%), and improved cognition (n¼11 studies; SMD¼1.74 [0.96e2.52]; P<0.0001; I 2 ¼94%) and cardiovascular function (n¼6 studies; SMD¼3.28 [1.96e4.59]; P<0.00001; I 2 ¼96%). Five of six studies demonstrated autonomic changes after vagal neuromodulation by measuring heart rate variability, muscle sympathetic nerve activity, or both. Conclusions: Indirect vagal neuromodulation improves physiological measures associated with limiting organ dysfunction, although studies are of low quality, are susceptible to bias and lack specific focus on perioperative patients.

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“…These results are consistent with previous studies. For example, auricular vagus nerve stimulation of aged rats subjected to surgery reduces postoperative levels of TNF-α, IL-1β and NF-κB and improves postoperative memory based on the Morris water maze [27]. Injecting the agomir miR-181b-5p in the hippocampus of mice before surgery down-regulates TNF-α, IL-1β, and monocyte chemoattractant protein-1, thereby reducing microglial activation and ameliorating hippocampus-dependent memory Note: F, forward primer; R, reverse primer.…”

Section: Discussionmentioning

confidence: 99%

Autophagy attenuates postoperative cognitive dysfunction by up-regulating cystatin C in aged rats undergoing splenectomy

Xing-hua

Long-yuan

Chang

et al. 2019

Preprint

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B ackground : This study aimed to explore whether autophagy can attenuate postoperative cognitive dysfunction (POCD) by up-regulating cystatin C (CysC) in aged rats undergoing splenectomy. Methods : Rats were randomized into four groups ( n = 10 per group): normal control (CON), surgery (SUR), surgery + rapamycin (autophagy inducer) at 1.0 mg/kg/d (RAP), and surgery + 3-methyladenine (autophagy inhibitor) at 3.0 mg/kg/d (3-MA). Treatments were carried out for four weeks. Postoperative learning and memory were assessed using the Morris water maze. Hippocampal expression of the autophagy-related proteins ATG5, LC-3B, Beclin1, and p62 as well as Cys C was assayed using Western blotting and real-time polymerase chain reaction. Results: SUR animals showed higher levels of autophagy and higher expression of autophagy proteins and Cys C than CON animals. These levels were even higher in RAP animals, which also showed lower levels of the inflammatory factors IL-1β, IL-6 and TNF-α than the other groups. Learning and memory functions were higher in RAP animals than in the other groups on days 5 and 7. Effects of 3-MA were opposite to those of RAP. Conclusion : Autophagy improves learning and memory in aged rats following splenectomy, which may involve up-regulation of Cys C and attenuation of neuro-inflammation.

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Auricular vagus nerve stimulation protects against postoperative cognitive dysfunction by attenuating neuroinflammation and neurodegeneration in aged rats

Cited by 28 publications

References 26 publications

The Vagal Autonomic Pathway of COVID-19 at the Crossroad of Alzheimer’s Disease and Aging: A Review of Knowledge

The Vagal Autonomic Pathway of COVID-19 at the Crossroad of Alzheimer’s Disease and Aging: A Review of Knowledge

The potential for autonomic neuromodulation to reduce perioperative complications and pain: a systematic review and meta-analysis

Autophagy attenuates postoperative cognitive dysfunction by up-regulating cystatin C in aged rats undergoing splenectomy

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