Can a basic solution activate the inflammatory reflex? A review of potential mechanisms, opportunities, and challenges

Alvarez, Milena Rodriguez; Alarcón, Juan Marcos; Roman, Christopher; Lazaro, Deana; Bobrowski-Khoury, Natasha; Baena-Caldas, Gloria Patricia; Esber, Guillem R.

doi:10.1016/j.phrs.2022.106525

Cited by 3 publications

(1 citation statement)

References 172 publications

(275 reference statements)

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“…Invasive and non-invasive stimulation of the cervical vagus nerve is used to modulate a great variety of conditions such as epileptic seizures (Muthiah et al, 2023), depression (Theiss and Slavin, 2022), gastrointestinal disorders (Payne et al, 2019), inflammation (Alvarez et al, 2022), heart failure (Konstam et al, 2022), migraine and other headaches (Straube and Eren, 2021). Hence, as the vagus nerve, especially in its cervical course, contains several groups of fibers, it is vital to understand what actually is stimulated by cervical vagus stimulation and how its effect is induced.…”

Section: Introductionmentioning

confidence: 99%

Sympathetic components in left and right human cervical vagus nerve: implications for vagus nerve stimulation

Ruigrok,

Mantel,

Orlandini

et al. 2023

Front. Neuroanat.

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Cervical vagus nerve stimulation is in a great variety of clinical situations indicated as a form of treatment. It is textbook knowledge that at the cervical level the vagus nerve contains many different fiber classes. Yet, recently, several reports have shown that this nerve also may contain an additional class of potentially noradrenergic fibers, suggested to denote efferent sympathetic fibers. As such, the nature and presence of these fibers should be considered when choosing a stimulation protocol. We have studied human vagus material extracted from dissection room cadavers in order to further confirm the presence of this class of fibers, to study their origin and direction within the nerve and to determine their distribution and variability between subjects and pairs of left and right nerves of the same individual. Sections were studied with immunohistochemical techniques using antibodies against tyrosine hydroxylase (TH: presumed to indicate noradrenergic fibers), myelin basic protein and neurofilament. Our results show that at least part of the TH-positive fibers derive from the superior cervical ganglion or sympathetic trunk, do not follow a cranial but take a peripheral course through the nerve. The portion of TH-positive fibers is highly variable between individuals but also between the left and right pairs of the same individual. TH-positive fibers can distribute and wander throughout the fascicles but maintain a generally clustered appearance. The fraction of TH-positive fibers generally diminishes in the left cervical vagus nerve when moving in a caudal direction but remains more constant in the right nerve. These results may help to determine optimal stimulation parameters for cervical vagus stimulation in clinical settings.

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Section: Introductionmentioning

confidence: 99%

Sympathetic components in left and right human cervical vagus nerve: implications for vagus nerve stimulation

Ruigrok,

Mantel,

Orlandini

et al. 2023

Front. Neuroanat.

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The immunomodulatory effect of oral NaHCO3 is mediated by the splenic nerve: multivariate impact revealed by artificial neural networks

Alvarez,

Alkaissi,

Rieger

et al. 2024

J Neuroinflammation

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Stimulation of the inflammatory reflex (IR) is a promising strategy for treating systemic inflammatory disorders. Recent studies suggest oral sodium bicarbonate (NaHCO3) as a potential activator of the IR, offering a safe and cost-effective treatment approach. However, the mechanisms underlying NaHCO3-induced anti-inflammatory effects remain unclear. We investigated whether oral NaHCO3’s immunomodulatory effects are mediated by the splenic nerve. Female rats received NaHCO3 or water (H2O) for four days, and splenic immune markers were assessed using flow cytometry. NaHCO3 led to a significant increase (p < 0.05, and/or partial eta squared > 0.06) in anti-inflammatory markers, including CD11bc + CD206 + (M2-like) macrophages, CD3 + CD4 + FoxP3 + cells (Tregs), and Tregs/M1-like ratio. Conversely, proinflammatory markers, such as CD11bc + CD38 + TNFα + (M1-like) macrophages, M1-like/M2-like ratio, and SSChigh/SSClow ratio of FSChighCD11bc + cells, decreased in the spleen following NaHCO3 administration. These effects were abolished in spleen-denervated rats, suggesting the necessity of the splenic nerve in mediating NaHCO3-induced immunomodulation. Artificial neural networks accurately classified NaHCO3 and H2O treatment in sham rats but failed in spleen-denervated rats, highlighting the splenic nerve's critical role. Additionally, spleen denervation independently influenced Tregs, M2-like macrophages, Tregs/M1-like ratio, and CD11bc + CD38 + cells, indicating distinct effects from both surgery and treatment. Principal component analysis (PCA) further supported the separate effects. Our findings suggest that the splenic nerve transmits oral NaHCO3-induced immunomodulatory changes to the spleen, emphasizing NaHCO3’s potential as an IR activator with therapeutic implications for a wide spectrum of systemic inflammatory conditions. Graphical abstract

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Gut microbiota: a potential influencer of insomnia occurring after COVID-19 infection

Fang,

Wang,

Liu

et al. 2024

Front. Psychiatry

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The prevalence of insomnia has increased in recent years, significantly affecting the lives of many individuals. Coronavirus disease 2019 (COVID-19) infection has been found to have a substantial impact on the human gut microbiota (GM). Clinical studies have shown that the high prevalence, prolonged duration, and refractory treatment of insomnia symptoms following the COVID-19 pandemic may be related to the effect of COVID-19 infection on the GM. Therefore, the GM may be a potential target for the treatment of insomnia following COVID-19 infection. However, relevant studies have not been well-documented, and the GM has not been sufficiently analyzed in the context of insomnia treatment. Herein, we review the interaction between sleep and the GM, summarize the characteristics of COVID-19-induced abnormal changes in the GM and metabolites in patients with insomnia, and discuss potential mechanisms, including metabolic, immune, and neural pathways, by which these abnormal changes in the GM cause insomnia as well as the factors affecting the GM. Finally, we discuss the prospect of modulating the host GM community for the effective treatment of insomnia after COVID-19 infection and the need for further clinical studies.

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Can a basic solution activate the inflammatory reflex? A review of potential mechanisms, opportunities, and challenges

Cited by 3 publications

References 172 publications

Sympathetic components in left and right human cervical vagus nerve: implications for vagus nerve stimulation

Sympathetic components in left and right human cervical vagus nerve: implications for vagus nerve stimulation

The immunomodulatory effect of oral NaHCO3 is mediated by the splenic nerve: multivariate impact revealed by artificial neural networks

Gut microbiota: a potential influencer of insomnia occurring after COVID-19 infection

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