Int J Mol Sci. 2024 Oct 17;25(20):11163. doi: 10.3390/ijms252011163.

ABSTRACT

Migraine is a prevalent neurological disorder, particularly among individuals aged 20-50 years, with significant social and economic impacts. Despite its high prevalence, the pathogenesis of migraine remains unclear. In this review, we provide a comprehensive overview of cortical spreading depolarization/depression (CSD) and its close association with migraine aura, focusing on its role in understanding migraine pathogenesis and therapeutic interventions. We discuss historical studies that have demonstrated the role of CSD in the visual phenomenon of migraine aura, along with modern imaging techniques confirming its propagation across the occipital cortex. Animal studies are examined to indicate that CSD is not exclusive to migraines; it also occurs in other neurological conditions. At the cellular level, we review how CSD is characterized by ionic changes and excitotoxicity, leading to neuronal and glial responses. We explore how CSD activates the trigeminal nervous system and upregulates the expression of calcitonin gene-related peptides (CGRP), thereby contributing to migraine pain. Factors such as genetics, obesity, and environmental conditions that influence the CSD threshold are discussed, suggesting potential therapeutic targets. Current treatments for migraine, including prophylactic agents and CGRP-targeting drugs, are evaluated in the context of their expected effects on suppressing CSD activity. Additionally, we highlight emerging therapies such as intranasal insulin-like growth factor 1 and vagus nerve stimulation, which have shown promise in reducing CSD susceptibility and frequency. By elucidating the molecular and cellular mechanisms of CSD, this review aims to enhance the understanding of migraine pathogenesis and support the development of targeted therapeutic strategies.

PMID:39456943 | DOI:10.3390/ijms252011163

Neurogastroenterol Motil. 2024 Oct 25:e14949. doi: 10.1111/nmo.14949. Online ahead of print.

ABSTRACT

BACKGROUND: Accumulating evidence has suggested that neuropeptides such as orexin, ghrelin, or oxytocin act centrally in the brain to regulate intestinal barrier function through the vagus nerve. It has been reported that the vagal cholinergic anti-inflammatory pathway was blocked by splenectomy. In the present study, we therefore examined the effect of splenectomy on neuropeptides-induced improvement of increased intestinal permeability.

METHODS: Colonic permeability was determined in vivo by quantifying the absorbed Evans blue in colonic tissue for 15 min spectrophotometrically in rats.

RESULTS: Splenectomy increased colonic permeability. The increased permeability by splenectomy was significantly blocked by vagal activation induced by carbachol or 2-deoxy-d-glucose which was prevented by atropine, suggesting vagal activation could prevent colonic hyperpermeability in splenectomized rats. In the splenectomized rats, intracisternal injection of orexin, ghrelin, oxytocin, or butyrate failed to inhibit increased colonic permeability while intracisternal glucagon-like peptide-1 (GLP-1) analogue, liraglutide, potently blocked the increased colonic permeability in a dose-dependent manner. The liraglutide-induced improvement of increased colonic permeability was blocked by atropine in splenectomized rats. Intracisternal injection of GLP-1 receptor antagonist attenuated 2-deoxy-d-glucose-induced improvement of colonic hyperpermeability in splenectomized rats.

CONCLUSION: The present results suggested that the spleen is important in the improvement of intestinal barrier function by brain orexin, ghrelin or oxytocin, and butyrate. On the other hand, GLP-1 acts centrally in the brain to improve colonic hyperpermeability in a spleen-independent manner. All these results suggest that dual mechanisms (spleen dependent or independent) may exist for the brain-gut regulation in intestinal barrier function.

PMID:39450642 | DOI:10.1111/nmo.14949

NPJ Parkinsons Dis. 2024 Oct 24;10(1):199. doi: 10.1038/s41531-024-00803-1.

ABSTRACT

Parkinson’s Disease (PD) is a prevalent, progressive neurodegenerative disease with motor and non-motor symptoms. Vagus Nerve Stimulation (VNS) has emerged as a potential therapeutic approach for PD, but published research on this topic varies widely. This scoping review maps existing literature on VNS for PD, highlighting stimulation methods, operational parameters, safety profiles, neurophysiological mechanisms, and clinical outcomes in human and animal models. Online databases were used to identify 788 papers published between 2013 and 2023, from which 17 publications on invasive and non-invasive VNS in PD were selected. Studies showed high variability in VNS parameters and study design. Evidence in animal models and human subjects suggests potential neurophysiological effects on PD-related pathology and motor function improvements. However, significant gaps in the literature remain. Future research should include rigorous reporting of study design, standardization of stimulation parameters, and larger sample sizes to ultimately facilitate translation of VNS into clinical practice.

PMID:39448636 | PMC:PMC11502766 | DOI:10.1038/s41531-024-00803-1

Diabetes Technol Ther. 2024 Oct 24. doi: 10.1089/dia.2024.0175. Online ahead of print.

ABSTRACT

Objective: Autonomic neuropathy is associated with dysglycemia that is difficult to control. We investigated if transcutaneous vagus nerve stimulation (tVNS) could improve glycemic levels. Methods: We randomized 145 individuals with type 1 diabetes (T1D) (n = 70) or type 2 diabetes (T2D) (n = 75) and diabetic autonomic neuropathy (DAN) to self-administered treatment with active cervical tVNS (n = 68) or sham (n = 77) for 1 week (4 daily stimulations) and 8 weeks (2 daily stimulations), separated by a wash-out period of at least 2 weeks. Continuous glucose monitoring (CGM) indices were measured for 104 participants starting 5 days prior to intervention periods, during the 1-week period, and at end of the 8-week period. Primary outcomes were between-group differences in changes in coefficient of variation (CV) and in time in range (TIR 3.9-10 mmol/L). Secondary outcomes were other metrics of CGM and HbA1c. Results: For the 1-week period, median [interquartile range] changes of CV from baseline to follow-up were -1.1 [-4.3;2.0] % in active and -1.5 [-4.4;2.5] % in sham, with no significance between groups (P = 0.54). For TIR, the corresponding changes were 2.4 [-2.1;7.4] % in active and 5.1 [-2.6;8.8] in sham group (P = 0.84). For the 8-week treatment period, changes in CV and TIR between groups were also nonsignificant. However, in the subgroup analysis, persons with T1D receiving active tVNS for 8 weeks had a significant reduction in CV compared with the T1D group receiving sham stimulation (estimated treatment effect: -11.6 [95% confidence interval -20.2;-2.0] %, P = 0.009). None of the changes in secondary outcomes between treatment groups were significantly different. Conclusions: Overall, no significant changes were observed in CGM metrics between treatment arms, while individuals with T1D and DAN decreased their CV after 8 weeks of tVNS treatment.

PMID:39446990 | DOI:10.1089/dia.2024.0175

Front Physiol. 2024 Oct 9;15:1452490. doi: 10.3389/fphys.2024.1452490. eCollection 2024.

ABSTRACT

OBJECTIVE: This systematic review aims to comprehensively analyze the efficacy and underlying mechanisms of vagus nerve stimulation (VNS) in enhancing cognitive functions and its therapeutic potential for various cognitive impairments. The review focuses on the impact of VNS on emotional processing, executive functions, learning, memory, and its clinical applications in conditions such as epilepsy, depression, Alzheimer’s disease, and other neurological disorders.

METHODS: A systematic search of electronic databases (PubMed, Scopus, Web of Science) was conducted using the keywords “vagus nerve stimulation,” “cognitive enhancement,” “emotional processing,” “executive function,” “learning and memory,” “epilepsy,” “depression,” “Alzheimer’s disease,” “neurological disorders,” “attention-deficit/hyperactivity disorder,” “sleep disorders,” and “long COVID.” The inclusion criteria encompassed controlled trials, longitudinal studies, and meta-analyses published in English between 2000 and July 2024.

RESULTS: A comprehensive review of 100 articles highlighted the cognitive effects of Vagus Nerve Stimulation (VNS). Studies show that VNS, especially through transcutaneous auricular VNS (taVNS), enhances emotional recognition, particularly for facial expressions, and improves selective attention under high cognitive demands. Additionally, VNS enhances learning and memory, including associative memory and spatial working memory tasks. In clinical applications, VNS exhibits promising benefits for improving cognitive functions in treatment-resistant epilepsy, depression, and Alzheimer’s disease.

CONCLUSION: VNS represents a promising therapeutic approach for enhancing cognitive function across diverse patient populations. The reviewed evidence highlights its efficacy in modulating cognitive domains in healthy individuals and improving cognition in neurological conditions. However, the comparative effectiveness of different VNS modalities and the differential effects of online versus offline VNS on cognitive psychology require further investigation. Future research should focus on optimizing VNS protocols and elucidating specific cognitive domains that benefit most from VNS interventions. This ongoing exploration is essential for maximizing the therapeutic potential of VNS in clinical practice.

PMID:39444752 | PMC:PMC11496278 | DOI:10.3389/fphys.2024.1452490

Front Hum Neurosci. 2024 Oct 8;18:1473535. doi: 10.3389/fnhum.2024.1473535. eCollection 2024.

ABSTRACT

PURPOSE: Long-term post-stroke cognitive impairment (PSCI) exhibits an accelerated rate of long-term cognitive decline, which can impair communication, limit social engagement, and increase rate of institutional dependence. The aim of this case report is to provide evidence for the potential of home-based transcutaneous auricular vagus nerve stimulation (taVNS) for home-bound patients with severe, long-term PSCI.

METHODS: A 71-year-old male suffered a stroke two and a half years ago, which imaging reported foci of cerebral infarction visible in the left temporal and parietal lobes. The patient was performed taVNS twice a day for 30 min, 5 times a week for 8 weeks. The patient was evaluated the changes of cognitive function and brain white matter at 4 time points: baseline (t0), 4 weeks without taVNS after baseline (t1), 4 weeks of intervention (t2), and 8 weeks of intervention (t3). The effect of taVNS on white matter changes was visualized by DTI.

RESULTS: After 8 weeks of taVNS treatment, the scores of Montreal cognitive assessment improved and the time to complete the shape trails test decreased. The DTI results showed that white matter in bilateral dorsal lateral prefrontal cortex remodeled after taVNS.

CONCLUSION: Eight-week home-based taVNS may be beneficial to long-term PSCI. Further studies of home-based taVNS treating patients with long-term PSCI are needed.

PMID:39444545 | PMC:PMC11497276 | DOI:10.3389/fnhum.2024.1473535

PM R. 2024 Oct 23. doi: 10.1002/pmrj.13268. Online ahead of print.

ABSTRACT

BACKGROUND: Autonomic rehabilitation using osteopathic manipulative treatment (OMT) to stimulate the vagus nerve may be a good adjunct therapy by physiatrists who treat dysautonomia. Heart rate variability (HRV) may provide quantitative evidence for the benefits of OMT on autonomic nervous system function. Elevated HRV indicates optimal health and reduced mortality risk, whereas low HRV is associated with stress, pain, and chronic disease pathology.

OBJECTIVE: To analyze the impact of modified occipitomastoid suture v-spread OMT technique on vagal tone by measuring HRV.

DESIGN: Within-participant design with 5-minute HRV measurement pre- and post-OMT treatment.

SETTING: Clinical examination suites.

PARTICIPANTS: Thirty healthy osteopathic medical students.

INTERVENTIONS: A modified occipitomastoid suture v-spread treating somatic dysfunction by osteopathic physicians trained in osteopathic neuromusculoskeletal medicine.

MAIN OUTCOME MEASURES: HRV variables related to vagal tone including root mean square of successive differences (RMSSD), percentage of successive normal sinus RR intervals >50 ms (pNN50), high frequency (HF), Parasympathetic Nervous System Index (PNSI), and Sympathetic Nervous System Index (SNSI). Repeated measures t-test analyzed the difference in mean HRV values after OMT.

RESULTS: There were statistically significant increases in each of the HRV measures after OMT. Participants had a mean (95% confidence interval) RMSSD of 50.5 ms (38.3-62.8) at baseline and 55.0 ms (41.2-68.7, p = .013) post-OMT. pNN50 was 24.5% (17.6-31.3, n = 30) at baseline and 28.2% (20.8-35.6, p = .003) post-OMT. HF was 1549.6 ms² (389.8-2709.4) at baseline and 1901.8 ms² (618.2-3185.4, p = .103) post-OMT. PNSI was -0.1 (-0.5 to 0.2) at baseline and 0.1 (-0.3 to 1.5, p < .01) post-OMT, and SNSI was 0.2 (-0.1 to 0.6) at baseline and 0.05 (-0.3 to 0.4, p < .01) post-OMT. Normalization, due to high baseline variance, results include RMSSD 1.1 ms (1.0 to 1.1, p = .012), pNN50 1.3 (1.1 to 1.4, p = .011), and HF 1.2 ms² (1.1 to 1.4, p = .018).

CONCLUSIONS: Modified occipitomastoid suture v-spread may provide clinical benefit through increased vagal tone and decreased sympathetic activity.

PMID:39444156 | DOI:10.1002/pmrj.13268

BMC Surg. 2024 Oct 23;24(1):327. doi: 10.1186/s12893-024-02635-5.

ABSTRACT

PURPOSE: Retraction of the hepatic left lateral segment (HLLS) is a crucial maneuver for surgical field exposure during laparoscopic gastrectomy with systematic lymphadenectomy. Though various methods of retraction are available, there is no perfect solution. Here, we report the results of our initial 42 cases with HLLS inversion method and discuss the feasibility, safety, effectiveness and technical aspects of this method.

METHODS: The intraoperative and postoperative short-term outcomes of 42 patients who underwent HLLS inversion during laparoscopic total gastrectomy and proximal gastrectomy in our department September, 2023 to January, 2024 were reviewed. HLLS inversion was performed by mobilizing the HLLS and inverting it to the right supra-hepatic space through an incision at the falciform ligament.

RESULTS: 42 patients underwent HLLS inversion successfully with an average time of 13.9 min. 7 patients needed re-inversion due to slipping back of the HLLS during operation. Optimal exposure of the surgical field was achieved in all patients. No intra-operative complications occurred, except for 1 patient presented with mild intraoperative hepatic hemorrhage requiring electrocoagulation for hemostasis. Alanine aminotransferase and glutamine aminotransferase elevated in some patients on postoperative day 1(POD1), but declined to preoperative levels on the 7th postoperative day. There were no Clavien-Dindo II grade or higher digestive complications after surgery. In 5 patients with preservation the hepatic branch of the vagus nerve, the contractile function of the gall bladder was intact or slightly impaired 2 weeks after operation.

CONCLUSION: For laparoscopic proximal gastrectomy (LPG) and laparoscopic total gastrectomy (LTG), HLLS inversion is a feasible method for optimizing visualization of the surgical field with preservation of the function of the hepatic branch of the vagus nerve. It is safe and acceptable as to the manipulation time. Re-inversion is easy and effective even in case of failure of inversion. HLLS inversion seems to be a promising technique for retraction of the liver during laparoscopic gastrectomy.

PMID:39443980 | DOI:10.1186/s12893-024-02635-5

Sci Rep. 2024 Oct 17;14(1):24391. doi: 10.1038/s41598-024-72179-4.

ABSTRACT

The efficacy of transcutaneous auricular vagus nerve stimulation (taVNS) as a non-invasive method to modulate physiological markers of noradrenergic activity of the Locus Coeruleus (LC), such as pupil dilation, is increasingly more discussed. However, taVNS studies show high heterogeneity of stimulation effects. Therefore, a taVNS setup was established here to test different frequencies (10 Hz and 25 Hz) and intensities (3 mA and 5 mA) during phasic stimulation (3 s) with time-synchronous recording of pupil dilation in younger adults. Specifically, phasic real taVNS and higher intensity led to increased pupil dilation, which is consistent with phasic invasive VNS studies in animals. The results also suggest that the influence of intensity on pupil dilation may be stronger than that of frequency. However, there was an attenuation of taVNS-induced pupil dilation when differences in perception of sensations were considered. Specifically, pupil dilation during phasic stimulation increased with perceived stimulation intensity. The extent to which the effect of taVNS induces pupil dilation and the involvement of sensory perception in the stimulation process are discussed here and require more extensive research. Additionally, it is crucial to strive for comparable stimulation sensations during systematic parameter testing in order to investigate possible effects of phasic taVNS on pupil dilation in more detail.

PMID:39420188 | PMC:PMC11487125 | DOI:10.1038/s41598-024-72179-4

ACS Pharmacol Transl Sci. 2024 Sep 9;7(10):3071-3085. doi: 10.1021/acsptsci.4c00270. eCollection 2024 Oct 11.

ABSTRACT

It is widely said that a healthy intestinal environment plays an essential role in better mental condition. One known dietary nutrient that maintains the intestinal environment is dietary fiber. A recent study showed that maintaining the intestinal environment with dietary fiber alleviated symptoms of psychiatric disorders in animals. However, such effects have only been reported with soluble fiber, which is highly fermentable and promotes short-chain fatty acid (SCFA) production, and not with insoluble fiber. Therefore, we aimed to verify whether insoluble fiber, such as cellulose, can alter emotion via changes in the gut. We divided mice into two groups and fed either a standard diet (SD, which contains both insoluble and soluble dietary fibers) or a cellulose-rich diet (CRD, which contains cellulose alone as the dietary fibers). We found that CRD-fed mice display increased anxiety-like behavior. CRD-fed animals also showed decreased intestinal SCFA levels along with increased intestinal permeability, dysmotility, and hypersensitivity. This behavioral and physiological effect of CRD has been completely abolished in vagotomized mice, indicating the direct link between intestinal environment exacerbation to the emotion through the gut-brain axis. Additionally, we found that amygdalar dopamine signaling has been modified in CRD-fed animals, and the opioid antagonist abolished this dopaminergic modification as well as CRD-induced anxiety. Altogether, our findings indicate that consumption of cellulose alone as the dietary fiber may evoke intestinal abnormalities, which fire the vagus nerve, then the opioidergic system, and amygdalar dopamine upregulation, resulting in the enhancement of anxiety.

PMID:39416961 | PMC:PMC11475280 | DOI:10.1021/acsptsci.4c00270