Int J Mol Sci. 2024 Jul 17;25(14):7831. doi: 10.3390/ijms25147831.

ABSTRACT

The vagus nerve regulates metabolic homeostasis and mediates gut-brain communication. We hypothesized that vagus nerve dysfunction, induced by truncated vagotomy (VGX) or carotid artery occlusion (AO), would disrupt gut-brain communication and exacerbate metabolic dysregulation, neuroinflammation, and cognitive impairment. This study aimed to test the hypothesis in gerbils fed a high-fat diet. The gerbils were divided into four groups: AO with VGX (AO_VGX), AO without VGX (AO_NVGX), no AO with VGX (NAO_VGX), and no AO without VGX (NAO_NVGX). After 5 weeks on a high-fat diet, the neuronal cell death, neurological severity, hippocampal lipids and inflammation, energy/glucose metabolism, intestinal morphology, and fecal microbiome composition were assessed. AO and VGX increased the neuronal cell death and neurological severity scores associated with increased hippocampal lipid profiles and lipid peroxidation, as well as changes in the inflammatory cytokine expression and brain-derived neurotrophic factor (BDNF) levels. AO and VGX also increased the body weight, visceral fat mass, and insulin resistance and decreased the skeletal muscle mass. The intestinal morphology and microbiome composition were altered, with an increase in the abundance of Bifidobacterium and a decrease in Akkermansia and Ruminococcus. Microbial metagenome functions were also impacted, including glutamatergic synaptic activity, glycogen synthesis, and amino acid biosynthesis. Interestingly, the effects of VGX were not significantly additive with AO, suggesting that AO inhibited the vagus nerve activity, partly offsetting the effects of VGX. In conclusion, AO and VGX exacerbated the dysregulation of energy, glucose, and lipid metabolism, neuroinflammation, and memory deficits, potentially through the modulation of the gut-brain axis. Targeting the gut-brain axis by inhibiting vagus nerve suppression represents a potential therapeutic strategy for ischemic stroke.

PMID:39063072 | DOI:10.3390/ijms25147831

Brain Sci. 2024 Jul 2;14(7):675. doi: 10.3390/brainsci14070675.

ABSTRACT

Epilepsy affects over 65 million people worldwide. One-third of people with epilepsy do not respond to medication and may benefit from surgery. Vagus nerve stimulation (VNS) is the first neuromodulation therapy for the treatment of drug-resistant epilepsy. This method is used in combination with anti-seizure medications in adults and in the pediatric population. VNS has also been demonstrated to have benefits for some epilepsy comorbidities, such as depression, and can be used in combination with other neuromodulation therapies in epilepsy. The authors present an overview of VNS physiology, patient selection, surgery and risks, neuromodulation therapy, and application to epilepsy comorbidities.

PMID:39061416 | DOI:10.3390/brainsci14070675

Brain Sci. 2024 Jun 26;14(7):639. doi: 10.3390/brainsci14070639.

ABSTRACT

Epilepsy treatment primarily involves antiseizure medications (ASMs) to eliminate seizures and improve the quality of life, but many patients develop drug-resistant epilepsy (DRE), necessitating alternative interventions. This study aimed to evaluate the long-term efficacy and safety of vagus nerve stimulation (VNS) in managing DRE. We retrospectively analyzed data from 105 adult patients treated at Agostino Gemelli Hospital from 1994 to 2022. Among the 73 patients with follow-up data, 80.8% were responders, experiencing significant reductions in seizure frequency over an average follow-up period of 9.4 years. Although 19.2% were non-responders, many of these patients still opted for generator replacements due to improvements in quality of life, such as fewer falls and shorter post-ictal periods. The overall complication rate was 12.3%, with most complications being mild and manageable. These findings suggest that VNS offers substantial long-term benefits for patients with DRE, improving seizure control and quality of life. This study underscores the importance of VNS as a viable long-term treatment option for DRE, highlighting its potential to significantly enhance patient outcomes and quality of life.

PMID:39061382 | DOI:10.3390/brainsci14070639

Brain Sci. 2024 Jul 10;14(7):690. doi: 10.3390/brainsci14070690.

ABSTRACT

Non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) has attracted increasing interest as a neurostimulation tool with potential applications in modulating cognitive processes such as attention and memory, possibly through the modulation of the locus-coeruleus noradrenaline system. Studies examining the P300 brain-related component as a correlate of noradrenergic activity, however, have yielded inconsistent findings, possibly due to differences in stimulation parameters, thus necessitating further investigation. In this event-related potential study involving 61 participants, therefore, we examined how changes in taVNS parameters, specifically stimulation type (interval vs. continuous stimulation) and duration, influence P300 amplitudes during a visual novelty oddball task. Although no effects of stimulation were found over the whole cluster and time window of the P300, cluster-based permutation tests revealed a distinct impact of taVNS on the P300 response for a small electrode cluster, characterized by larger amplitudes observed for easy targets (i.e., stimuli that are easily discernible from standards) following taVNS compared to sham stimulation. Notably, our findings suggested that the type of stimulation significantly modulated taVNS effects on the P300, with continuous stimulation showing larger P300 differences (taVNS vs. sham) for hard targets and standards compared to interval stimulation. We observed no interaction effects of stimulation duration on the target-related P300. While our findings align with previous research, further investigation is warranted to fully elucidate the influence of taVNS on the P300 component and its potential utility as a reliable marker for neuromodulation in this field.

PMID:39061430 | DOI:10.3390/brainsci14070690

J Clin Med. 2024 Jul 22;13(14):4267. doi: 10.3390/jcm13144267.

ABSTRACT

Background: Evidence suggests that vagus nerve stimulation can modulate heart rate variability (HRV). However, there is a lack of mechanistic studies in healthy subjects assessing the effects of bilateral transcutaneous auricular vagus nerve stimulation (taVNS) on HRV. Our study aims to investigate how taVNS can influence the HRV response, including the influence of demographic variables in this response. Methods: Therefore, we conducted a randomized controlled study with 44 subjects, 22 allocated to active and 22 to sham taVNS. Results: Our results showed a significant difference between groups in the high-frequency (HF) metric. Active taVNS increased the HF metric significantly as compared to sham taVNS. Also, we found that age was a significant effect modifier of the relationship between taVNS and HF-HRV, as a larger increase in HF-HRV was seen in the older subjects. Importantly, there was a decrease in HF-HRV in the sham group. Conclusions: These findings suggest that younger subjects can adapt and maintain a constant level of HF-HRV regardless of the type of stimulation, but in the older subjects, only the active taVNS recipients were able to maintain and increase their HF-HRV. These results are important because they indicate that taVNS can enhance physiological regulation processes in response to external events.

PMID:39064307 | DOI:10.3390/jcm13144267

J Clin Med. 2024 Jul 14;13(14):4114. doi: 10.3390/jcm13144114.

ABSTRACT

Background: Evaluating the differential impact of vagus nerve stimulation (VNS) therapy across various seizure types, our study explores its efficacy specifically in patients with categorized minor and major seizures. Methods: We conducted a retrospective cohort study involving 76 patients with pharmacoresistant epilepsy treated at the University Emergency Hospital of Bucharest between 2021 and 2024. Seizures were classified as ‘minor’ (including focal-aware and non-motor/absence seizures) and ‘major’ (including focal to bilateral tonic-clonic and generalized motor seizures), based on modified International League Against Epilepsy (ILAE) criteria. This classification allowed us to assess the response to VNS therapy, defined by a 50% or greater reduction in seizure frequency at the 12-month follow-up. Results: Our findings reveal that major seizures respond more favorably to VNS therapy, significantly reducing both frequency and intensity. In contrast, minor seizures showed a less pronounced response in frequency reduction but noted improvements in neurocognitive functions, suggesting a nuanced benefit of VNS in these cases. Conclusion: The study underscores the importance of seizure type in determining the efficacy of VNS therapy, advocating for personalized treatment approaches based on seizure classification. This approach could potentially enhance clinical outcomes by tailoring VNS settings to specific seizure types, improving overall management strategies in pharmacoresistant epilepsy.

PMID:39064154 | DOI:10.3390/jcm13144114

Nutrients. 2024 Jul 11;16(14):2222. doi: 10.3390/nu16142222.

ABSTRACT

This review summarizes the relationship between diet, the gut microbiome, and migraine. Key findings reveal that certain dietary factors, such as caffeine and alcohol, can trigger migraine, while nutrients like magnesium and riboflavin may help alleviate migraine symptoms. The gut microbiome, through its influence on neuroinflammation (e.g., vagus nerve and cytokines), gut-brain signaling (e.g., gamma-aminobutyric acid), and metabolic function (e.g., short-chain fatty acids), plays a crucial role in migraine susceptibility. Migraine can also alter eating behaviors, leading to poor nutritional choices and further exacerbating the condition. Individual variability in diet and microbiome composition highlights the need for personalized dietary and prebiotic interventions. Epidemiological and clinical data support the effectiveness of tailored nutritional approaches, such as elimination diets and the inclusion of beneficial nutrients, in managing migraine. More work is needed to confirm the role of prebiotics, probiotics, and potentially fecal microbiome translation in the management of migraine. Future research should focus on large-scale studies to elucidate the underlying mechanisms of bidirectional interaction between diet and migraine and develop evidence-based clinical guidelines. Integrating dietary management, gut health optimization, and lifestyle modifications can potentially offer a holistic approach to reducing migraine frequency and severity, ultimately improving patient outcomes and quality of life.

PMID:39064664 | DOI:10.3390/nu16142222

Nutrients. 2024 Jul 21;16(14):2366. doi: 10.3390/nu16142366.

ABSTRACT

Alzheimer’s disease is the most common cause of dementia globally. The pathogenesis is multifactorial and includes deposition of amyloid-β in the central nervous system, presence of intraneuronal neurofibrillary tangles and a decreased amount of synapses. It remains uncertain what causes the progression of the disease. Nowadays, it is suggested that the brain is connected to the gastrointestinal tract, especially the enteric nervous system and gut microbiome. Studies have found a positive association between AD and gastrointestinal diseases such as periodontitis, Helicobacter pylori infection, inflammatory bowel disease and microbiome disorders. H. pylori and its metabolites can enter the CNS via the oropharyngeal olfactory pathway and may predispose to the onset and progression of AD. Periodontitis may cause systemic inflammation of low severity with high levels of pro-inflammatory cytokines and neutrophils. Moreover, lipopolysaccharide from oral bacteria accompanies beta-amyloid in plaques that form in the brain. Increased intestinal permeability in IBS leads to neuronal inflammation from transference. Chronic inflammation may lead to beta-amyloid plaque formation in the intestinal tract that spreads to the brain via the vagus nerve. The microbiome plays an important role in many bodily functions, such as nutrient absorption and vitamin production, but it is also an important factor in the development of many diseases, including Alzheimer’s disease. Both the quantity and diversity of the microbiome change significantly in patients with AD and even in people in the preclinical stage of the disease, when symptoms are not yet present. The microbiome influences the functioning of the central nervous system through, among other things, the microbiota-gut-brain axis. Given the involvement of the microbiome in the pathogenesis of AD, antibiotic therapy, probiotics and prebiotics, and faecal transplantation are being considered as possible therapeutic options.

PMID:39064809 | DOI:10.3390/nu16142366

Sci Rep. 2024 Jul 26;14(1):17177. doi: 10.1038/s41598-024-68015-4.

ABSTRACT

Transcutaneous vagus nerve stimulation (tVNS) is a promising technique for enhancing cognitive performance and skill acquisition. Yet, its efficacy for enhancing learning rate and long-term retention in an ecologically valid learning environment has not been demonstrated. We conducted two double-blind sham-controlled experiments examining the efficacy of auricular tVNS (taVNS: Experiment (1) and cervical tVNS (tcVNS: Experiment (2), on a 5 day second-language vocabulary acquisition protocol among highly selected career linguists at the US Department of Defense’s premier language school. tcVNS produced accelerated recall performance during training (Day 2-4), benefits of which were maintained across a 24 h retention interval with no stimulation at the final test. Consistent with prior work, tcVNS also produced fatigue-mitigating and focus-promoting effects as measured by the Air Force Research Laboratory Mood Questionnaire. Based on the current and the previous findings supporting tVNS’ efficacy on performance, training enhancement, and fatigue mitigation, we believe tcVNS to be an effective learning acceleration tool that can be utilized at language-teaching and other institutions focused on intensive training of cognitive skills.

PMID:39060415 | DOI:10.1038/s41598-024-68015-4

Childs Nerv Syst. 2024 Jul 26. doi: 10.1007/s00381-024-06546-x. Online ahead of print.

ABSTRACT

PURPOSE: To assess responsive neurostimulation (RNS) efficacy in pediatric patients with drug-resistant epilepsy, comparing response (≥ 50% reduction in seizure frequency) rates between patients with two or fewer seizure foci and those with multifocal or generalized epilepsy. This study seeks to address the gap in knowledge regarding RNS effectiveness in pediatric populations.

METHODS: A systematic review and meta-analysis included data from PubMed, Embase, and Web of Science through November 2023, including 17 retrospective studies and a case series of 24 patients from our practice for a total of 105 aggregated patients. The inclusion criteria of patients were age $\le$ 18 and diagnosis of DRE. Exclusion criteria were nonhuman subjects and cases where RNS was not utilized to treat DRE. Study inclusion criteria were detailing the use of RNS and comparing patients with $\le$ 2 foci with other focalities. Study exclusion criteria were failure to specify RNS lead placement or type of epilepsy. The risk of bias was assessed using the ROBINS-I tool for all non-randomized studies. Effect sizes and variances were aggregated to provide a comprehensive measure of RNS efficacy, and heterogeneity among the studies was assessed using I² statistics and Cochran’s Q test to evaluate the consistency of the findings. Statistical analyses were conducted using IBM SPSS. We analyzed demographics, epilepsy history, treatment outcomes, and RNS details using descriptive and inferential statistics, including Wilcoxon-Mann-Whitney, Fisher’s exact, and chi-squared tests. This systematic review was not registered.

RESULTS: Seventeen retrospective studies and a single-institution case series, encompassing 105 pediatric patients, were analyzed. Effect sizes and confidence intervals were calculated to quantify treatment effects. Analyses revealed that RNS reduces seizure frequency across a spectrum of pediatric epilepsy syndromes, irrespective of the seizures’ focal, multifocal, or generalized origins. The effectiveness of RNS was not influenced by the patient’s sex, age at epilepsy onset, or presence of neurological and psychiatric comorbidities. Prior vagus nerve stimulation surgery and the presence of an epileptic syndrome were factors associated with a lower likelihood of near-complete seizure remission with RNS, underscoring the complexities of treating patients with generalized epilepsies or previous interventional failures. The necessity of further research into individualized surgical strategies for patients was underscored by the mixed results of comparisons of electrode characteristics with responder rates. Limitations of our study include its reliance on retrospective studies, which introduces potential bias and limits the ability to infer causality.

DISCUSSION: RNS is a safe and effective treatment in pediatric patients with DRE across demographic, comorbidity, and focality variability. FDA age and focality restrictions, along with patient and physician hesitancy, may be limiting the potential for effective treatment of pediatric DRE with RNS. Prospective randomized trials are recommended to validate these findings.

PMID:39060746 | DOI:10.1007/s00381-024-06546-x