Anat Cell Biol. 2024 Jul 17. doi: 10.5115/acb.24.052. Online ahead of print.

ABSTRACT

The recurrent laryngeal nerve is a bilateral branch of the vagus nerve that is mainly associated with the motor innervation of the intrinsic muscles of the larynx. Despite its bilateral distribution, the right and left recurrent laryngeal nerves display unequal length due to embryological processes related to the development of the aortic arches. This length asymmetry leads to theories about morphological compensations to provide symmetrical functions to the intrinsic muscles of the larynx. In this study we investigated the developmental and cross-sectional morphometrics of the recurrent laryngeal nerves in human fetuses. Fifteen stillbirth fetuses donated to anatomical and medical research were used for investigation. Fetuses had intrauterine age ranging from 30 to 40 weeks estimated by biometry methods. Specialized anatomical dissection of the visceral block of the neck was performed to prepare histological samples of the recurrent laryngeal nerves in its point of contact with the larynx, and morpho-quantitative techniques were applied to evaluate the epineurium and perineural space of the recurrent laryngeal nerves. No statistical difference in the cross-sectional morphology of the epineurium and perineural space between right and left recurrent laryngeal nerves intra-individually was confirmed, however, we found evidence that these structures are under greater development in the left recurrent laryngeal nerve during 30 to 40 weeks of intrauterine life. Our data suggest that the nerves are under morphological development that possibly set the stage for accommodation of larger diameter and myelinization of the left recurrent laryngeal nerve during post-natal life.

PMID:39013797 | DOI:10.5115/acb.24.052

Gut Microbes. 2024 Jan-Dec;16(1):2371950. doi: 10.1080/19490976.2024.2371950. Epub 2024 Jul 15.

ABSTRACT

The gut microbial ecosystem communicates bidirectionally with the brain in what is known as the gut-microbiome-brain axis. Bidirectional signaling occurs through several pathways including signaling via the vagus nerve, circulation of microbial metabolites, and immune activation. Alterations in the gut microbiota are implicated in Alzheimer’s disease (AD), a progressive neurodegenerative disease. Perturbations in gut microbial communities may affect pathways within the gut-microbiome-brain axis through altered production of microbial metabolites including ɣ-aminobutyric acid (GABA), the primary inhibitory mammalian neurotransmitter. GABA has been shown to act on gut integrity through modulation of gut mucins and tight junction proteins and may be involved in vagus nerve signal inhibition. The GABAergic signaling pathway has been shown to be dysregulated in AD, and may be responsive to interventions. Gut microbial production of GABA is of recent interest in neurological disorders, including AD. Bacteroides and Lactic Acid Bacteria (LAB), including Lactobacillus, are predominant producers of GABA. This review highlights how temporal alterations in gut microbial communities associated with AD may affect the GABAergic signaling pathway, intestinal barrier integrity, and AD-associated inflammation.

PMID:39008552 | PMC:PMC11253888 | DOI:10.1080/19490976.2024.2371950

Bio Protoc. 2024 Jul 5;14(13):e5022. doi: 10.21769/BioProtoc.5022. eCollection 2024 Jul 5.

ABSTRACT

Vascular cognitive impairment (VCI) is a syndrome defined as cognitive decline caused by vascular disease and is associated with various types of dementia. Chronic cerebral hypoperfusion (CCH) is one of the major contributors to VCI. Among the various rodent models used to study CCH-induced VCI, we have found the mouse bilateral common carotid artery stenosis (BCAS) model to be highly suitable. Here, we introduce the BCAS model of C57BL/6J mice generated using microcoils with an internal diameter of 0.18 mm. To produce the mouse BCAS model, the bilateral common carotid arteries are isolated from the adhering tissues and vagus nerves and twined around the microcoils. This model shows cognitive impairment and white matter lesions preceding neuronal dysfunction around postoperative day 28, which is similar to the human clinical picture. Overall, the mouse BCAS model will continue to be useful in studying CCH-induced VCI. Key features • This mouse BCAS model requires approximately 4 weeks to show phenotypes such as cognitive impairment and white matter injury.

PMID:39007157 | PMC:PMC11238111 | DOI:10.21769/BioProtoc.5022

Int J Mol Sci. 2024 Jun 26;25(13):6959. doi: 10.3390/ijms25136959.

ABSTRACT

Observed and recorded in various forms since ancient times, ‘syncope’ is often popularly called ‘fainting’, such that the two terms are used synonymously. Syncope/fainting can be caused by a variety of conditions, including but not limited to head injuries, vertigo, and oxygen deficiency. Here, we draw on a large body of literature on syncope, including the role of a recently discovered set of specialized mammalian neurons. Although the etiology of syncope still remains a mystery, we have attempted to provide a comprehensive account of what is known and what still needs to be performed. Much of our understanding of syncope is owing to studies in the laboratory mouse, whereas evidence from human patients remains scarce. Interestingly, the cardioinhibitory Bezold-Jarisch reflex, recognized in the early 1900s, has an intriguing similarity to-and forms the basis of-syncope. In this review, we have integrated this minimal model into the modern view of the brain-neuron-heart signaling loop of syncope, to which several signaling events contribute. Molecular signaling is our major focus here, presented in terms of a normal heart, and thus, syncope due to abnormal or weak heart activity is not discussed in detail. In addition, we have offered possible directions for clinical intervention based on this model. Overall, this article is expected to generate interest in chronic vertigo and syncope/fainting, an enigmatic condition that affects most humans at some point in life; it is also hoped that this may lead to a mechanism-based clinical intervention in the future.

PMID:39000068 | DOI:10.3390/ijms25136959

Psychophysiology. 2024 Jul 12:e14650. doi: 10.1111/psyp.14650. Online ahead of print.

ABSTRACT

The neurovisceral integration model proposes that information flows bidirectionally between the brain and the heart via the vagus nerve, indexed by vagally mediated heart rate variability (vmHRV). Voluntary reduction in breathing rate (slow-paced breathing, SPB, 5.5 Breathing Per Minute (BPM)) can enhance vmHRV. Additionally, prefrontal transcranial direct current stimulation (tDCS) can modulate the excitability of the prefrontal region and influence the vagus nerve. However, research on the combination of SPB and prefrontal tDCS to increase vmHRV and other cardiac (heart rate (HR) and blood pressure) and peripheral (skin conductance) indices is scarce. We hypothesized that the combination of 20 min of SPB and prefrontal tDCS would have a greater effect than each intervention in isolation. Hence, 200 participants were divided into four groups: active tDCS with SPB, active tDCS with 15 BPM breathing, sham tDCS with SPB, and sham tDCS with 15 BPM breathing. Regardless of the tDCS condition, the 5.5 BPM group showed a significant increase in vmHRV over 20 minutes and significant decreases in HR at the first and second 5-min epochs of the intervention. Regardless of breathing condition, the active tDCS group exhibited higher HR at the fourth 5-min epoch of the intervention than the sham tDCS group. No other effects were observed. Overall, SPB is a robust technique for increasing vmHRV, whereas prefrontal tDCS may produce effects that counteract those of SPB. More research is necessary to test whether and how SPB and neuromodulation approaches can be combined to improve cardiac vagal tone.

PMID:38997945 | DOI:10.1111/psyp.14650

Medicine (Baltimore). 2024 Jul 12;103(28):e38802. doi: 10.1097/MD.0000000000038802.

ABSTRACT

BACKGROUND AND AIMS: To develop a model that describes how the pancreas functions, how the rate of synthesis of digestive enzymes is regulated, and finally what puts the pancreas to rest between meals.

METHODS: We applied the principals of control theory to previously published canine data to develop a model for how the canine pancreas functions. Using this model, we then describe the steps needed to apply this model to the human pancreas.

RESULTS: This new closed-loop negative feedback model describes what regulates digestive enzyme synthesis. This model is based on basolateral exocytosis of butyrylcholinesterase (BCHE) into the interstitial space. It is this level of BCHE * BCHE activity that controls the rate of canine pancreas digestive enzyme synthesis, and in the absence of stimulation from the vagus nerve, puts the pancreas to rest between meals.

CONCLUSIONS: Finding secretagogue-specific inhibitory enzymes in the human pancreas that are analogous to BCHE in the canine, and blocking its associated receptors, may lead to a cure for human pancreatitis.

PMID:38996137 | DOI:10.1097/MD.0000000000038802

Front Psychiatry. 2024 Jun 27;15:1393549. doi: 10.3389/fpsyt.2024.1393549. eCollection 2024.

ABSTRACT

BACKGROUND: Maternal exposure to inflammation is one of the causes of autism spectrum disorder (ASD). Electrical stimulation of the vagus nerve exerts a neuroprotective effect via its anti-inflammatory action. We thus investigated whether transcutaneous auricular vagus nerve stimulation (taVNS) can enhance social abilities in a mouse model of ASD induced by maternal immune activation (MIA).

METHODS: ASD mouse model were constructed by intraperitoneal injection of polyinosinic:polycytidylic acid (poly (I:C)). TaVNS with different parameters were tested in ASD mouse model and in C57BL/6 mice, then various behavioral tests and biochemical analyses related to autism were conducted. ASD model mice were injected with an interleukin (IL)-17a antibody into the brain, followed by behavioral testing and biochemical analyses.

RESULTS: TaVNS reduced anxiety, improved social function, decreased the number of microglia, and inhibited M1 polarization of microglia. Additionally, taVNS attenuated the expression of the IL-17a protein in the prefrontal cortex and blood of ASD model mice. To examine the possible involvement of IL-17a in taVNS-induced neuroprotection, we injected an IL-17a antibody into the prefrontal cortex of ASD model mice and found that neutralizing IL-17a decreased the number of microglia and inhibited M1 polarization. Furthermore, neutralizing IL-17a improved social function in autism model mice.

CONCLUSION: Our study revealed that reduced neuroinflammation is an important mechanism of taVNS-mediated social improvement and neuroprotection against autism. This effect of taVNS could be attributed to the inhibition of the IL-17a pathway.

PMID:38993386 | PMC:PMC11237520 | DOI:10.3389/fpsyt.2024.1393549

Exp Neurobiol. 2024 Jun 30;33(3):129-139. doi: 10.5607/en24012.

ABSTRACT

Cancer chemotherapy often triggers peripheral neuropathy in patients, leading to neuropathic pain in the extremities. While previous research has explored various nerve stimulation to alleviate chemotherapy-induced peripheral neuropathy (CIPN), evidence on the effectiveness of noninvasive auricular vagus nerve stimulation (aVNS) remains uncertain. This study aimed to investigate the efficacy of non-invasive aVNS in relieving CIPN pain. To induce CIPN in experimental animals, oxaliplatin was intraperitoneally administered to rats (6 mg/kg). Mechanical and cold allodynia, the representative symptoms of neuropathic pain, were evaluated using the von Frey test and acetone test, respectively. The CIPN animals were randomly assigned to groups and treated with aVNS (5 V, square wave) at different frequencies (2, 20, or 100 Hz) for 20 minutes. Results revealed that 20 Hz aVNS exhibited the most pronounced analgesic effect, while 2 or 100 Hz aVNS exhibited weak effects. Immunohistochemistry analysis demonstrated increased c-Fos expression in the locus coeruleus (LC) in the brain of CIPN rats treated with aVNS compared to sham treatment. To elucidate the analgesic mechanisms involving the adrenergic descending pathway, α₁-, α₂-, or β-adrenergic receptor antagonists were administered to the spinal cord before 20 Hz aVNS. Only the β-adrenergic receptor antagonist, propranolol, blocked the analgesic effect of aVNS. These findings suggest that 20 Hz aVNS may effectively alleviate CIPN pain through β-adrenergic receptor activation.

PMID:38993080 | DOI:10.5607/en24012

Inflammopharmacology. 2024 Jul 11. doi: 10.1007/s10787-024-01510-2. Online ahead of print.

ABSTRACT

“Path to a good mood lies through the gut.” This statement seems to imply that it has long been believed that the gut is connected with the brain. Research has shown that eating food activates the reward system and releases dopamine (DA), establishing a link between the peripheral and central nervous system. At the same time, researchers also trust that the gut is involved in the onset of many diseases, including Parkinson’s disease (PD), in which gastrointestinal dysfunction is considered a prevalent symptom. Reports suggest that PD starts from the gut and reaches the brain via the vagus nerve. Recent studies have revealed an intriguing interaction between the gut and brain, which links gut dysbiosis to the etiology of PD. This review aims to explore the mechanistic pathway how reactive oxygen species (ROS) generation in the gut affects the makeup and operation of the dopamine circuitry in the brain. Our primary concern is ROS generation in the gut, which disrupts the gut microbiome (GM), causing α-synuclein accumulation and inflammation. This trio contributes to the loss of DA neurons in the brain, resulting in PD development. This review also compiles pre-clinical and clinical studies on antioxidants, demonstrating that antioxidants reduce ROS and increase DA levels. Collectively, the study highlights the necessity of comprehending the gut-brain axis for unraveling the riddles of PD pathogenesis and considering new therapeutic approaches.

PMID:38992324 | DOI:10.1007/s10787-024-01510-2

Neurophysiol Clin. 2024 Jul 10;54(5):102996. doi: 10.1016/j.neucli.2024.102996. Online ahead of print.

ABSTRACT

Vagus nerve stimulation (VNS) is an effective neuromodulatory treatment for patients with drug resistant epilepsy who cannot undergo curative surgical resection. Safety information states that the use of radiofrequency ablation devices may damage the VNS generator and leads. However, documented cases are scarce. This 62-year-old patient with bitemporal lobe epilepsy treated with VNS underwent radiofrequency ablation of an atrial fibrillation without any perioperative or postoperative complications.

PMID:38991469 | DOI:10.1016/j.neucli.2024.102996