The immunomodulatory effect of oral NaHCO 3 is mediated by the splenic nerve: multivariate impact revealed by artificial neural networks

Stimulation of the inflammatory reflex (IR) is a promising strategy for treating systemic inflammatory disorders. Recent studies suggest oral sodium bicarbonate (NaHCO ) as a potential activator of the IR, offering a safe and cost-effective treatment approach. However, the mechanisms underlying NaHC...

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Bibliographic Details
Published in:Journal of neuroinflammation 2024-03, Vol.21 (1), p.79
Main Authors: Alvarez, Milena Rodriguez, Alkaissi, Hussam, Rieger, Aja M, Esber, Guillem R, Acosta, Manuel E, Stephenson, Stacy I, Maurice, Allison V, Valencia, Laura Melissa Rodríguez, Roman, Christopher A, Alarcon, Juan Marcos
Format: Article
Language:English
Subjects:
Animals
Anti-Inflammatory Agents - pharmacology
Female
Immunomodulation
Macrophages
Rats
Spleen
Vagus Nerve
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Summary:Stimulation of the inflammatory reflex (IR) is a promising strategy for treating systemic inflammatory disorders. Recent studies suggest oral sodium bicarbonate (NaHCO ) as a potential activator of the IR, offering a safe and cost-effective treatment approach. However, the mechanisms underlying NaHCO -induced anti-inflammatory effects remain unclear. We investigated whether oral NaHCO 's immunomodulatory effects are mediated by the splenic nerve. Female rats received NaHCO or water (H O) for four days, and splenic immune markers were assessed using flow cytometry. NaHCO led to a significant increase (p  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 SSC /SSC ratio of FSC CD11bc + cells, decreased in the spleen following NaHCO administration. These effects were abolished in spleen-denervated rats, suggesting the necessity of the splenic nerve in mediating NaHCO -induced immunomodulation. Artificial neural networks accurately classified NaHCO and H O 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 NaHCO -induced immunomodulatory changes to the spleen, emphasizing NaHCO 's potential as an IR activator with therapeutic implications for a wide spectrum of systemic inflammatory conditions.
ISSN:1742-2094