Neurosci Lett. 2024 Mar 20:137737. doi: 10.1016/j.neulet.2024.137737. Online ahead of print.

ABSTRACT

Extracranial waste transport from the brain interstitial fluid to the deep cervical lymph node (dCLN) is not extensively understood. The present study aims to show the cranial nerves that have a role in the transport of brain lymphatics vessels (LVs), their localization, diameter, and number using podoplanin (PDPN) and CD31 immunohistochemistry (IHC) and Western blotting. Cranial nerve samples from 6 human cases (3 cadavers, and 3 autopsies) were evaluated for IHC and 3 autopsies for Western blotting. The IHC staining showed LVs along the optic, olfactory, oculomotor, trigeminal, facial, glossopharyngeal, accessory, and vagus nerves. However, no LVs present along the trochlear, abducens, vestibulocochlear, and hypoglossal nerves. The LVs were predominantly localized at the endoneurium of the cranial nerve that has motor components, and LVs in the cranial nerves that had sensory components were present in all 3 layers. The number of LVs accompanying the olfactory, optic, and trigeminal nerves was classified as numerous; oculomotor, glossopharyngeal, vagus, and accessory was moderate; and facial nerves was few. The largest diameter of LVs was in the epineurium and the smallest one was in the endoneurium. The majority of Western blotting results correlated with the IHC. The present findings suggest that specific cranial nerves with variable quantities provide a pathway for the transport of wastes from the brain to dCLN. Thus, the knowledge of the transport of brain lymphatics along cranial nerves may help understand the pathophysiology of various neurological diseases.

PMID:38519013 | DOI:10.1016/j.neulet.2024.137737

Brain Spine. 2023 Dec 14;4:102733. doi: 10.1016/j.bas.2023.102733. eCollection 2024.

ABSTRACT

INTRODUCTION: Vagus nerve stimulation (VNS) is the most frequently used neuromodulation treatment for Drug-Resistant Epilepsy (DRE) patients. Complications of VNS surgery include surgical site infection and unilateral vocal cord paresis. Complication rates vary across studies.

RESEARCH QUESTION: What is the safety profile of VNS related surgeries?

MATERIALS AND METHODS: Retrospective cohort study using patient files of DRE-patients who had undergone primary implantation of a VNS-system, replacement of the VNS pulse generator, replacement of the lead, replacement of both pulse generator and lead, or VNS removal surgery in the Maastricht UMC+. Multiple Imputation was used for missing data. Univariable and multivariable logistic regression analysis were performed to analyze possible risk factors, in case of a small sample size, an independent-samples t-test and Fisher’s exact test or Pearson’s X²-test were used. The complication rate was calculated as percentage.

RESULTS: This study included a total of 606 VNS surgical procedures, leading to 67 complications of which 3 permanent complications. Complication rate after primary implantation was 13.4%; 2,5% for pulse generator replacement; 21.4% for lead revision and 27.3% for complete VNS removal. No statistically significant results were found when analyzing the results of adults and children <18 years separately.

DISCUSSION AND CONCLUSION: Complication rates of VNS-related surgeries in our own institutional series are low and comparable to previously reported series. VNS surgery is a relatively safe procedure. The complication rate differs per type of surgery and mean surgery duration was longer for patients with complications after lead revision surgery compared to patients without complications.

PMID:38510607 | PMC:PMC10951712 | DOI:10.1016/j.bas.2023.102733

Inflammopharmacology. 2024 Mar 21. doi: 10.1007/s10787-024-01446-7. Online ahead of print.

ABSTRACT

The gut and the brain communicate bidirectionally through the autonomic nervous system. The vagus nerve is a key component of this gut-brain axis, and has numerous properties such as anti-inflammatory, antinociceptive, anti-depressive effects. A perturbation of this gut-brain communication is involved in the pathogeny of functional digestive disorders, such as irritable bowel syndrome, and inflammatory bowel diseases. Stress plays a role in the pathogeny of these diseases, which are biopsychosocial models. There are presently unmet needs of pharmacological treatments of these chronic debilitating diseases. Treatments are not devoid of side effects, cost-effective, do not cure the diseases, can lose effects over time, thus explaining the poor satisfaction of patients, their lack of compliance, and their interest for non-drug therapies. The gut-brain axis can be targeted for therapeutic purposes in irritable bowel syndrome and inflammatory bowel disease through non-drug therapies, such as hypnosis and vagus nerve stimulation, opening up possibilities for responding to patient expectations.

PMID:38512653 | DOI:10.1007/s10787-024-01446-7

Auton Neurosci. 2024 Mar 4;253:103162. doi: 10.1016/j.autneu.2024.103162. Online ahead of print.

ABSTRACT

Vagus nerve stimulation (VNS) is under clinical investigation as a therapy for heart failure with reduced ejection fraction (HFrEF). This study aimed to investigate its therapeutic effects on three main components of heart failure: cardiac function, cardiac remodeling and central neuroinflammation using a pressure overload (PO) rat model. Male Sprague-Dawley rats were divided into four groups: PO, PO + VNS, PO + VNS sham, and controls. All rats, except controls, underwent a PO surgery to constrict the thoracic aorta (~50 %) to induce HFrEF. Open loop VNS therapy was continuously administered to PO + VNS rats at 20 Hz, 1.0 mA for 60 days. Evaluation of cardiac function and structure via echocardiograms showed decreases in stroke volume and relative ejection fraction and increases in the internal diameter of the left ventricle during systole and diastole in PO rats (p < 0.05). However, these PO-induced adverse changes were alleviated with VNS therapy. Additionally, PO rats exhibited significant increases in myocyte cross sectional areas indicating hypertrophy, along with significant increases in myocardial fibrosis and apoptosis, all of which were reversed by VNS therapy (p < 0.05). Furthermore, VNS mitigated microglial activation in two central autonomic nuclei: the paraventricular nucleus of the hypothalamus and locus coeruleus. These findings demonstrate that when VNS therapy is initiated at an early stage of HFrEF progression (<10 % reduction in relative ejection fraction), the supplementation of vagal activity is effective in restoring multi organ homeostasis in a PO model.

PMID:38513382 | DOI:10.1016/j.autneu.2024.103162

Neuroscience. 2024 Mar 19:S0306-4522(24)00126-X. doi: 10.1016/j.neuroscience.2024.03.013. Online ahead of print.

ABSTRACT

Heart rate variability (HRV),a measure of the fluctuations in the intervals between consecutive heartbeats, is an indicator of changes in the autonomic nervous system. A chronic reduction in HRV has been repeatedly linked to clinical depression. However, the chronological and mechanistic aspects of this relationship, between the neural, physiological, and psychopathological levels, remain unclear. In this review we present evidence by which changes in HRV might precede the onset of depression. We describe several pathways that can facilitate this relationship. First, we examine a theoretical model of the impact of autonomic imbalance on HRV and its role in contributing to mood dysregulation and depression. We then highlight brain regions that are regulating both HRV and emotion, suggesting these neural regions as potential mediators of this relationship, and the Insula in particular. We also present additional possible mediating mechanisms involving the immune system and inflammation processes. Lastly, we support this model by showing evidence that modification of HRV with biofeedback leads to an improvement in some depression symptoms. The possibility that changes in HRV precede the onset of depression is a critical possibility to put to the test, not only because it will provide insights into the mechanisms of the illness but also because it may offer a predictive anddiagnosticphysiological marker for depression. Importantly, it may then also help develop new effective clinical interventions for the treatment of depression.

PMID:38513761 | DOI:10.1016/j.neuroscience.2024.03.013

Phys Med Rehabil Clin N Am. 2024 May;35(2):369-382. doi: 10.1016/j.pmr.2023.06.008. Epub 2023 Aug 21.

ABSTRACT

Neural stimulation technology aids stroke survivors in regaining lost motor functions. This article explores its applications in upper and lower limb stroke rehabilitation. The authors review various methods to target the corticomotor system, including transcranial direct current stimulation, repetitive transcranial magnetic stimulation, and vagus nerve stimulation. In addition, the authors review the use of peripheral neuromuscular electrical stimulation for therapeutic and assistive purposes, including transcutaneous electrical nerve stimulation, neuromuscular electrical stimulation, and functional electrical stimulation. For each, the authors examine the potential benefits, limitations, safety considerations, and FDA status.

PMID:38514224 | DOI:10.1016/j.pmr.2023.06.008

Physiol Rep. 2024 Mar;12(6):e15981. doi: 10.14814/phy2.15981.

ABSTRACT

Reports on autonomic responses to transcutaneous auricular vagus nerve stimulation (taVNS) and osteopathic manipulative techniques have been equivocal, partly due to inconsistent interpretation of heart rate variability (HRV). We developed a mechanistic framework for the interpretation of HRV based on a model of sinus node automaticity that considers autonomic effects on Phase 3 repolarization and Phase 4 depolarization of the sinoatrial action potential. The model was applied to HRV parameters calculated from ECG recordings (healthy adult humans, both genders) before (30 min), during (15 min), and after (30 min) a time control intervention (rest, n = 23), taVNS (10 Hz, 300 μs, 1-2 mA, cymba concha, left ear, n = 12), or occipitoatlantal decompression (OA-D, n = 14). The experimental protocol was repeated on 3 consecutive days. The model simulation revealed that low frequency (LF) HRV best predicts sympathetic tone when calculated from heart rate time series, while high frequency (HF) HRV best predicts parasympathetic tone when calculated from heart period time series. Applying our model to the HRV responses to taVNS and OA-D, revealed that taVNS increases cardiac parasympathetic tone, while OA-D elicits a mild decrease in cardiac sympathetic tone.

PMID:38508860 | PMC:PMC10954510 | DOI:10.14814/phy2.15981

Epilepsia. 2024 Mar 20. doi: 10.1111/epi.17961. Online ahead of print.

ABSTRACT

Racial disparities affect multiple dimensions of epilepsy care including epilepsy surgery. This study aims to further explore these disparities by determining the utilization of invasive neuromodulation devices according to race and ethnicity in a multicenter study of patients living with focal drug-resistant epilepsy (DRE). We performed a post hoc analysis of the Human Epilepsy Project 2 (HEP2) data. HEP2 is a prospective study of patients living with focal DRE involving 10 sites distributed across the United States. There were no statistical differences in the racial distribution of the study population compared to the US population using census data except for patients reporting more than one race. Of 154 patients enrolled in HEP2, 55 (36%) underwent invasive neuromodulation for DRE management at some point in the course of their epilepsy. Of those, 36 (71%) were patients who identified as White. Patients were significantly less likely to have a device if they identified solely as Black/African American than if they did not (odds ratio = .21, 95% confidence interval = .05-.96, p = .03). Invasive neuromodulation for management of DRE is underutilized in the Black/African American population, indicating a new facet of racial disparities in epilepsy care.

PMID:38506370 | DOI:10.1111/epi.17961

J Cardiothorac Surg. 2024 Mar 19;19(1):136. doi: 10.1186/s13019-024-02627-9.

ABSTRACT

BACKGROUND: A right-sided aortic arch is a rare congenital vascular structure variation. Right lobectomy is not commonly performed on patients with such a condition. Further, there are no reports on lobectomy under uniportal video-assisted thoracoscopic surgery (VATS) in this patient group.

CASE PRESENTATION: A 67-year-old man with a right-sided aortic arch and Kommerell diverticulum underwent right upper lobectomy with mediastinal lymph node dissection under uniportal VATS for primary lung cancer. Due to the right descending aorta, which narrows the space of the dorsal hilum, handling of the stapler for stapling the right upper lobe bronchus from the uniport in the 6th intercostal space at the medial axillary line can be challenging. This issue was resolved by manipulating the staple over the azygos vein toward the inferior margin of the aortic arch. Via mediastinal lymphadenectomy, we found that the right recurrent laryngeal nerve branched from the right vagus nerve and hooked around the right-sided aortic arch.

CONCLUSIONS: Right lobectomy with mediastinal lymph node dissection under uniportal VATS can be performed for lung cancer in patients with a right-sided aortic arch.

PMID:38504342 | DOI:10.1186/s13019-024-02627-9

Acta Pharmacol Sin. 2024 Mar 19. doi: 10.1038/s41401-024-01245-4. Online ahead of print.

ABSTRACT

Ischemic stroke is a major cause of disability and death worldwide, and its management requires urgent attention. Previous studies have shown that vagus nerve stimulation (VNS) exerts neuroprotection in ischemic stroke by inhibiting neuroinflammation and apoptosis. In this study, we evaluated the timing for VNS intervention in ischemic stroke, and the underlying mechanisms of VNS-induced neuroprotection. Mice were subjected to transient middle cerebral artery occlusion (tMCAO) for 60 min. The left vagus nerve at cervical level was exposed and attached to an electrode connected to a low-frequency electrical stimulator. Vagus nerve stimulation (VNS) was given for 60 min before, during and after tMCAO (Pre-VNS, Dur-VNS, Post-VNS). Neurological function was assessed 24 h after reperfusion. We found that all the three VNS significantly protected against the tMCAO-induced injury evidenced by improved neurological function and reduced infarct volume. Moreover, the Pre-VNS was the most effective against the ischemic injury. We found that tMCAO activated microglia in the ischemic core and penumbra regions of the brain, followed by the NLRP3 inflammasome activation-induced neuroinflammation, which finally triggered neuronal death. VNS treatment preserved α7nAChR expression in the penumbra regions, inhibited NLRP3 inflammasome activation and ensuing neuroinflammation, rescuing cerebral neurons. The role of α7nAChR in microglial NLRP3 inflammasome activation in ischemic stroke was further validated using genetic manipulations, including Chrna7 knockout mice and microglial Chrna7 overexpression mice, as well as pharmacological interventions using the α7nAChR inhibitor methyllycaconitine and agonist PNU-282987. Collectively, this study demonstrates the potential of VNS as a safe and effective strategy to treat ischemic stroke, and presents a new approach targeting microglial NLRP3 inflammasome, which might be therapeutic for other inflammation-related diseases.

PMID:38504011 | DOI:10.1038/s41401-024-01245-4