Minimally invasive vagus nerve stimulation modulates mast cell degranulation via the microbiota-gut-brain axis to ameliorate blood-brain barrier and intestinal barrier damage following ischemic stroke

Int Immunopharmacol. 2024 Apr 10;132:112030. doi: 10.1016/j.intimp.2024.112030. Online ahead of print.

ABSTRACT

Mast cells (MCs) play a significant role in various diseases, and their activation and degranulation can trigger inflammatory responses and barrier damage. Several studies have indicated that vagus nerve stimulation (VNS) exerts ameliorates neurological injury, and regulates gut MC degranulation. However, there is limited research on the modulatory effect of VNS on MCs in both the gut and brain in brain ischemia-reperfusion (I/R) injury in this process. We aim to develop a minimally invasive, targeted and convenient VNS approach to assess the impact of VNS and to clarify the relationship between VNS and MCs on the prognosis of acute ischemic stroke. We utilized middle cerebral artery occlusion/reperfusion (MCAO/r) to induce brain I/R injury. After the experiment, the motor function and neurofunctional impairments of the rats were detected, and the gastrointestinal function, blood-brain barrier (BBB) and intestinal barrier damage, and systemic and local inflammation were evaluated by Nissl, TTC staining, Evans blue, immunofluorescence staining, transmission electron microscopy, western blot assays, ELISA, and fecal 16S rRNA sequencing methods. Our research confirmed that our minimally invasive VNS method is a novel approach for stimulating the vagus nerve. VNS alleviated motor deficits and gastrointestinal dysfunction while also suppressing intestinal and neuroinflammation. Additionally, VNS ameliorated gut microbiota dysbiosis in rats. Furthermore, our analysis indicated that VNS reduces chymase secretion by modulating MCs degranulation and improves intestinal and BBB damage. Our results showed that VNS treatment can alleviate the damage of BBB and colonic barrier after cerebral I/R by modulating mast cell degranulation, and alleviates systemic inflammatory responses.

PMID:38603861 | DOI:10.1016/j.intimp.2024.112030

Effect of transcranial direct current stimulation combined with transcutaneous auricular vagus nerve stimulation on poststroke cognitive impairment: a study protocol for a randomised controlled trial

BMJ Open. 2024 Apr 10;14(4):e082764. doi: 10.1136/bmjopen-2023-082764.

ABSTRACT

INTRODUCTION: Poststroke cognitive impairment is a common complication in stroke survivors, seriously affecting their quality of life. Therefore, it is crucial to improve cognitive function of patients who had a stroke. Transcranial direct current stimulation (tDCS) and transcutaneous auricular vagus nerve stimulation (taVNS) are non-invasive, safe treatments with great potential to improve cognitive function in poststroke patients. However, further improvements are needed in the effectiveness of a single non-invasive brain stimulation technique for cognitive rehabilitation. This study protocol aims to investigate the effect and neural mechanism of the combination of tDCS and taVNS on cognitive function in patients who had a stroke.

METHODS AND ANALYSIS: In this single-centre, prospective, parallel, randomised controlled trial, a total of 66 patients with poststroke cognitive impairment will be recruited and randomly assigned (1:1:1) to the tDCS group, the taVNS group and the combination of tDCS and taVNS group. Each group will receive 30 min of treatment daily, five times weekly for 3 weeks. Primary clinical outcome is the Montreal Cognitive Assessment. Secondary clinical outcomes include the Mini-Mental State Examination, Stroop Colour Word Test, Trail Marking Test, Symbol Digit Modalities Test and Modified Barthel Index. All clinical outcomes, functional MRI and diffusion tensor imaging will be measured at preintervention and postintervention.

ETHICS AND DISSEMINATION: The trial has been approved by the Ethics Committee of the First Affiliated Hospital of Yangtze University (approval no: KY202390). The results will be submitted for publication in peer-reviewed journals or at scientific conferences.

TRIAL REGISTRATION NUMBER: ChiCTR2300076632.

PMID:38604630 | DOI:10.1136/bmjopen-2023-082764

The Effects of Heart Rhythm Meditation on Vagal Tone and Well-being: A Mixed Methods Research Study

Appl Psychophysiol Biofeedback. 2024 Apr 12. doi: 10.1007/s10484-024-09639-0. Online ahead of print.

ABSTRACT

Many studies have examined the effects of meditation practice focused on the normal breath on vagal tone with mixed results. Heart Rhythm Meditation (HRM) is a unique meditation form that engages in the deep slow full breath, and puts the focus of attention on the heart. This form of breathing likely stimulates the vagus nerve with greater intensity. The purpose of this study was (a) to examine how the practice of HRM affects vagal activity as measured by heart rate variability (HRV); and (b) to examine how it affects participants’ well-being. 74 participants signed consent agreeing to: (a) take a six-week course to learn the practice of HRM; (b) engage in a daily practice for 10 weeks; (c) have their heart rate variability read through ECG technology and to take two validated well-being instruments at the beginning and end of the 10 weeks; and (d) participate in a focus group interview examining their perceptions of how the practice affected their well-being. 48 participants completed the study. Quantitative findings show the effect of the practice of HRM approached significance for multiple measures of HRV and vagal tone. An increase in well-being scores for those who did the meditation more than 10-minutes per day did meet statistical significance. Qualitative data indicate: (a) the positive effects of HRM on stress and well-being; (b) the development of a more expanded sense of self; and (c) an increased awareness of the interconnection of the body-heart-emotions and HRM’s role in emotion regulation.

PMID:38605265 | DOI:10.1007/s10484-024-09639-0

The Impact of Inflammation on Thermal Hyperpnea: Relevance for Heat Stress and Febrile Seizures

Am J Respir Cell Mol Biol. 2024 Apr 10. doi: 10.1165/rcmb.2023-0451OC. Online ahead of print.

ABSTRACT

Extreme heat caused by climate change is increasing transmission of infectious diseases resulting in a sharp rise in heat-related illness and mortality. Understanding mechanistic link between heat, inflammation and disease is thus important for public health. Thermal hyperpnea, and consequent respiratory alkalosis is crucial in febrile seizures and convulsions induced by heat stress in humans. Here we address what causes thermal hyperpnea in neonates and how is it affected by inflammation. TRPV1, a heat-activated channel is sensitized by inflammation and modulates breathing, and thus may play a key role. To investigate whether inflammatory sensitization of TRPV1 modifies neonatal ventilatory responses to heat stress, leading to respiratory alkalosis and an increased susceptibility to hyperthermic seizures we treated neonatal rats with bacterial lipopolysaccharide, and breathing, arterial pH, in-vitro vagus nerve activity, and seizure susceptibility were assessed during heat stress in the presence or absence of a TRPV1 antagonist (AMG-9810) or shRNA-mediated TRPV1 suppression. Lipopolysaccharide-induced inflammatory preconditioning lowered the threshold temperature and latency of hyperthermic seizures. This was accompanied by increased tidal volume, minute ventilation, expired CO2, and arterial pH (alkalosis). Lipopolysaccharide exposure also elevated vagal spiking and intracellular calcium levels in response to hyperthermia. TRPV1 inhibition with AMG-9810 or shRNA reduced the lipopolysaccharide-induced susceptibility to hyperthermic seizures and altered the breathing pattern to fast shallow breaths (tachypnea), making each breath less efficient and restoring arterial pH. These results indicate that inflammation exacerbates thermal hyperpnea-induced respiratory alkalosis associated with increased susceptibility to hyperthermic seizures, primarily mediated by TRPV1 localized to vagus neurons.

PMID:38597725 | DOI:10.1165/rcmb.2023-0451OC

Tumor ablation including carotid artery resection and simultaneous reconstruction: A retrospective study

J Craniomaxillofac Surg. 2024 Mar 26:S1010-5182(24)00116-1. doi: 10.1016/j.jcms.2024.03.033. Online ahead of print.

ABSTRACT

The study purpose is to review the surgical approach and evaluate the results in cases of head and neck malignancies with internal carotid artery invasion. The anatomical site of the primary tumor varied including a fixed massive metastatic neck disease of an occult intraoral carcinoma of the right tonsil, a recurrent metastatic neck tumor after laryngectomy for glottic primary carcinoma and a metastatic malignant melanoma of an unknown primary origin. In all cases carotid artery was invaded and therefore resected. An extended Javid shunt was performed between common carotid artery (CCA) and internal carotid artery (ICA) followed by CCA grafting with an interposition saphenous vein graft. In one case the vagus nerve was also grafted with an interposition sural graft. The total patient number was three. By clinical examination, follow-up and duplex scanning, the patency of the carotid grafts, vascular and non-vascular complications, disease recurrence and survival were analysed. Additionally, there was a double metachronous reconstruction for recurrence, giving the opportunity to study the graft adoption and response to disease. Internal carotid artery invasion portends a poor prognosis. The results show that carotid artery resection followed by the appropriate reconstruction yields a chance for cure or can provide reasonable palliation.

PMID:38582678 | DOI:10.1016/j.jcms.2024.03.033

Preservation of the celiac branch of the vagus nerve reduces the incidence of postoperative diarrhea in gastric cancer: a cohort study

World J Surg Oncol. 2024 Apr 6;22(1):87. doi: 10.1186/s12957-024-03370-0.

ABSTRACT

BACKGROUND: To investigate the short-term and long-term outcomes of preserving the celiac branch of the vagus nerve during laparoscopic distal gastrectomy.

METHODS: A total of 149 patients with prospective diagnosis of gastric cancer who underwent laparoscopic-assisted distal gastrectomy (LADG) combined with Billroth-II anastomosis and D2 lymph node dissection between 2017 and 2018 were retrospectively analyzed. The patients were divided into the preserved LADG group (P-LADG, n = 56) and the resected LADG group (R-LADG, n = 93) according to whether the vagus nerve celiac branch was preserved. We selected 56 patients (P-LADG, n = 56) with preservation of the celiac branch of the vagus nerve and 56 patients (R-LADG, n = 56) with removal of the celiac branch of the vagus nerve by propensity-matched score method. Postoperative nutritional status, weight change, short-term and long-term postoperative complications, and gallstone formation were evaluated in both groups at 5 years of postoperative follow-up. The status of residual gastritis and bile reflux was assessed endoscopically at 12 months postoperatively.

RESULTS: The incidence of diarrhea at 5 years postoperatively was lower in the P-LADG group than in the R-LADG group (p < 0.05). In the multivariate logistic analysis, the removal of vagus nerve celiac branch was an independent risk factor for the occurrence of postoperative diarrhea (odds ratio = 3.389, 95% confidential interval = 1.143-10.049, p = 0.028). In the multivariate logistic analysis, the removal of vagus nerve celiac branch was an independent risk factor for the occurrence of postoperative diarrhea (odds ratio = 4.371, 95% confidential interval = 1.418-13.479, p = 0.010).

CONCLUSIONS: Preservation of the celiac branch of the vagus nerve in LADG reduced the incidence of postoperative diarrhea postoperatively in gastric cancer.

TRIAL REGISTRATION: This study was registered with the Ethics Committee of the First Affiliated Hospital of Dalian Medical University in 2014 under the registration number: LCKY2014-04(X).

PMID:38582834 | DOI:10.1186/s12957-024-03370-0

Pylorus-preserving gastrectomy for early gastric cancer

World J Gastrointest Oncol. 2024 Mar 15;16(3):653-658. doi: 10.4251/wjgo.v16.i3.653.

ABSTRACT

Pylorus-preserving gastrectomy (PPG) has been widely accepted as a function-preserving gastrectomy for middle-third early gastric cancer (EGC) with a distal tumor border at least 4 cm proximal to the pylorus. The procedure essentially preserves the function of the pyloric sphincter, which requires to preserve the upper third of the stomach and a pyloric cuff at least 2.5 cm. The suprapyloric and infrapyloric vessels are usually preserved, as are the hepatic and pyloric branches of the vagus nerve. Compared with distal gastrectomy, PPG has significant advantages in preventing dumping syndrome, body weight loss and bile reflux gastritis. The postoperative complications after PPG have reached an acceptable level. PPG can be considered a safe, effective, and superior choice in EGC, and is expected to be extensively performed in the future.

PMID:38577445 | PMC:PMC10989389 | DOI:10.4251/wjgo.v16.i3.653

Hepatic interoception in health and disease

Auton Neurosci. 2024 Mar 29;253:103174. doi: 10.1016/j.autneu.2024.103174. Online ahead of print.

ABSTRACT

The liver is a large organ with crucial functions in metabolism and immune defense, as well as blood homeostasis and detoxification, and it is clearly in bidirectional communication with the brain and rest of the body via both neural and humoral pathways. A host of neural sensory mechanisms have been proposed, but in contrast to the gut-brain axis, details for both the exact site and molecular signaling steps of their peripheral transduction mechanisms are generally lacking. Similarly, knowledge about function-specific sensory and motor components of both vagal and spinal access pathways to the hepatic parenchyma is missing. Lack of progress largely owes to controversies regarding selectivity of vagal access pathways and extent of hepatocyte innervation. In contrast, there is considerable evidence for glucose sensors in the wall of the hepatic portal vein and their importance for glucose handling by the liver and the brain and the systemic response to hypoglycemia. As liver diseases are on the rise globally, and there are intriguing associations between liver diseases and mental illnesses, it will be important to further dissect and identify both neural and humoral pathways that mediate hepatocyte-specific signals to relevant brain areas. The question of whether and how sensations from the liver contribute to interoceptive self-awareness has not yet been explored.

PMID:38579493 | DOI:10.1016/j.autneu.2024.103174

Clinical characteristics and treatment exposure of patients with marked treatment-resistant unipolar major depressive disorder: A RECOVER trial report

Brain Stimul. 2024 Apr 2:S1935-861X(24)00052-4. doi: 10.1016/j.brs.2024.03.016. Online ahead of print.

ABSTRACT

BACKGROUND: RECOVER is a randomized sham-controlled trial of vagus nerve stimulation and the largest such trial conducted with a psychiatric neuromodulation intervention.

OBJECTIVE: To describe pre-implantation baseline clinical characteristics and treatment history of patients with unipolar, major depressive disorder (MDD), overall and as a function of exposure to interventional psychiatric treatments (INTs), including electroconvulsive therapy, transcranial magnetic stimulation, and esketamine.

METHODS: Medical, psychiatric, and treatment records were reviewed by study investigators and an independent Study Eligibility Committee prior to study qualification. Clinical characteristics and treatment history (using Antidepressant Treatment History [Short] Form) were compared in those qualified (N = 493) versus not qualified (N = 228) for RECOVER, and among the qualified group as a function of exposure to INTs during the current major depressive episode (MDE).

RESULTS: Unipolar MDD patients who qualified for RECOVER had marked TRD (median of 11.0 lifetime failed antidepressant treatments), severe disability (median WHODAS score of 50.0), and high rate of baseline suicidality (77% suicidal ideation, 40% previous suicide attempts). Overall, 71% had received at least 1 INT. Compared to the no INT group, INT recipients were younger and more severely depressed (QIDS-C, QIDS-SR), had greater suicidal ideation, earlier diagnosis of MDD, and failed more antidepressant medication trials.

CONCLUSIONS: RECOVER-qualified unipolar patients had marked TRD and marked treatment resistance with most failing 1 or more prior INTs. Treatment with ≥1 INTs in the current MDE was associated with earlier age of MDD onset, more severe clinical presentation, and greater treatment resistance relative to patients without a history of INT.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT03887715.

PMID:38574853 | DOI:10.1016/j.brs.2024.03.016