Vagus Nerve Stimulation Improves Mitochondrial Dysfunction in Post–cardiac Arrest Syndrome in the Asphyxial Cardiac Arrest Model in Rats

Kim, Seonghye; Park, Inwon; Lee, Jae Hyuk; Kim, Serin; Jang, Dong-Hyun; Jo, You Hwan

doi:10.3389/fnins.2022.762007

Cited by 4 publications

(2 citation statements)

References 49 publications

(66 reference statements)

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“…Brain injury after CA is a major cause of poor prognosis in patients. Therefore, the ultimate goal of CPR is the recovery of brain function [31,32]. Previous studies have shown that the dysregulation of TWEAK/Fn14 is associated with the pathophysiology of the neurodegeneration-related disorders [33].…”

Section: Discussionmentioning

confidence: 99%

TWEAK Knockdown Alleviates Post-Cardiac Arrest Brain Injury via the p38 MAPK/NF-κB Pathway

Zhang¹,

Wang²

2023

Discovery Medicine

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Background: Cardiac arrest (CA) and subsequent cardiopulmonary resuscitation (CPR) can cause brain injury, which is one of the factors affecting the recovery of brain function in CA patients. There is increasing evidence that tumor necrosis factorlike weak apoptosis-inducing factor (TWEAK) is associated with the brain injury diseases. This study was aimed to investigate the modulation mechanism of TWEAK involved in brain injury after cardiac arrest/subsequent cardiopulmonary resuscitation (CA/CPR). Materials and Methods: For in vivo experiments, healthy male Sprague-Dawley (SD) rats were applied to establish CA/CPR model, and oxygen-glucose deprivation/reoxygenation (OGD/R)-stimulated neurons model was established in vitro. TWEAK short hairpin RNAs (shRNAs) were injected into the lateral ventricle of CA/CPR rats or transfected into OGD/R cell culture to analyze the consequent alteration in neurological scores, behavioral tests, cell proliferation, cell apoptosis, and neuroinflammation through immunofluorescence staining, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining and enzyme linked immunosorbent assay (ELISA). Results: There were high expressions of TWEAK and fibroblast growth factor-inducible 14 (Fn14) in the cerebral cortex of CA/CPR rats and OGD/R-stimulated neuronal cells. TWEAK knockdown attenuated cell apoptosis, inflammation and showed better behavioral tests in CA/CPR rats. Furthermore, TWEAK shRNAs obviously facilitated cell proliferation, suppressed apoptosis and inflammation after OGD/R injury. Western blotting results stated that TWEAK silencing promoted phosphorylated p38 (p-p38) and phosphorylated p65 (p-p65) expressions. Conclusions: TWEAK might be involved in the pathogenesis of CA/CPR through inhibiting p38 MAPK/NF-κB pathway.

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Section: Discussionmentioning

confidence: 99%

TWEAK Knockdown Alleviates Post-Cardiac Arrest Brain Injury via the p38 MAPK/NF-κB Pathway

Zhang¹,

Wang²

2023

Discovery Medicine

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“…NaHCO3-treated rats showed improved mitochondrial mass and respiration during running exercise [144], and elevated PGC-1α mRNA-the protein product of which is associated with mitochondrial biogenesis-after chronic intense exercise [145]. For its part, iVNS has been shown to have a beneficial effect on cardiac mitochondrial respiration during sepsis [146], post-cardiac arrest syndrome in an asphyxial cardiac arrest model in rats [147], and myocardial ischemia [148]. Furthermore, the protective effect of VNS on myocardial injury during endotoxemia is mediated by a7nAChRs [149,150], identifying mitochondrial respiration as a target of IR activation.…”

Section: Nahco3 and Ir Activators: Metabolic Pathwaysmentioning

confidence: 99%

Can a basic solution activate the inflammatory reflex? A review of potential mechanisms, opportunities, and challenges

Alvarez

Alarcón

Roman

et al. 2023

Pharmacological Research

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Vagal nerve stimulation in myocardial ischemia/reperfusion injury: from bench to bedside

Giannino,

Nocera,

Andolfatto

et al. 2024

Bioelectron Med

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The identification of acute cardioprotective strategies against myocardial ischemia/reperfusion (I/R) injury that can be applied in the catheterization room is currently an unmet clinical need and several interventions evaluated in the past at the pre-clinical level have failed in translation. Autonomic imbalance, sustained by an abnormal afferent signalling, is a key component of I/R injury. Accordingly, there is a strong rationale for neuromodulation strategies, aimed at reducing sympathetic activity and/or increasing vagal tone, in this setting. In this review we focus on cervical vagal nerve stimulation (cVNS) and on transcutaneous auricular vagus nerve stimulation (taVNS); the latest has the potential to overcome several of the issues of invasive cVNS, including the possibility of being used in an acute setting, while retaining its beneficial effects. First, we discuss the pathophysiology of I/R injury, that is mostly a consequence of the overproduction of reactive oxygen species. Second, we describe the functional anatomy of the parasympathetic branch of the autonomic nervous system and the most relevant principles of bioelectronic medicine applied to electrical vagal modulation, with a particular focus on taVNS. Then, we provide a detailed and comprehensive summary of the most relevant pre-clinical studies of invasive and non-invasive VNS that support its strong cardioprotective effect whenever there is an acute or chronic cardiac injury and specifically in the setting of myocardial I/R injury. The potential benefit in the emerging field of post cardiac arrest syndrome (PCAS) is also mentioned. Indeed, electrical cVNS has a strong anti-adrenergic, anti-inflammatory, antioxidants, anti-apoptotic and pro-angiogenic effect; most of the involved molecular pathways were already directly confirmed to take place at the cardiac level for taVNS. Pre-clinical data clearly show that the sooner VNS is applied, the better the outcome, with the possibility of a marked infarct size reduction and almost complete left ventricular reverse remodelling when VNS is applied immediately before and during reperfusion. Finally, we describe in detail the limited but very promising clinical experience of taVNS in I/R injury available so far.

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Vagus Nerve Stimulation Improves Mitochondrial Dysfunction in Post–cardiac Arrest Syndrome in the Asphyxial Cardiac Arrest Model in Rats

Cited by 4 publications

References 49 publications

TWEAK Knockdown Alleviates Post-Cardiac Arrest Brain Injury via the p38 MAPK/NF-κB Pathway

TWEAK Knockdown Alleviates Post-Cardiac Arrest Brain Injury via the p38 MAPK/NF-κB Pathway

Can a basic solution activate the inflammatory reflex? A review of potential mechanisms, opportunities, and challenges

Vagal nerve stimulation in myocardial ischemia/reperfusion injury: from bench to bedside

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