Neural Reflex Control of Inflammation During Sepsis Syndromes

Fernández, Ricardo; Acuña-Castillo, Claudio

doi:10.5772/50283

Cited by 6 publications

(4 citation statements)

References 128 publications

(116 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Immune cells such as neutrophils and lymphocytes are innervated and regulated by the autonomic nerve according to the needs of the body's immunity [ 26 ]; sympathetic nerves have little effect on the number of lymphocytes [ 27 ], so the early inflammatory storm of sepsis should involve with the dysfunction of the autonomic nerve system, especially the vagus nerve. Therefore, CAP, as a key means of regulating the inflammation and immunity by the vagus nerve [ 28 ], plays a very important role of regulating inflammation and lymphocytes through the action on α 7nAChR receptors by acetylcholine released from its terminals.…”

Section: Discussionmentioning

confidence: 99%

Exploring the Mechanism on the Medullary Visceral Zone Inhibiting the Cholinergic Anti-inflammatory Pathway Induced by Sepsis

Zhou

Zhao³

et al. 2020

Mediators of Inflammation

View full text Add to dashboard Cite

Inflammatory storm is an important pathological mechanism of multiple organ dysfunction, and it is associated with most deaths in septic patients, deserving to be studied. Recent findings have confirmed that the Medullary Visceral Zone (MVZ) regulates inflammation and immunity through the cholinergic anti-inflammatory pathway (CAP), but how sepsis affects the MVZ and leads to uncontrolled inflammation remain unclear. The current study reported that sepsis induced MVZ to inhibit CAP which underlies the inflammation storm. Our studies have shown that the rat models of sepsis prepared by cecal ligation and puncture had a higher inflammatory level, higher mortality, and higher Murine Sepsis Score. In septic rats, some indicators of heart rate variability (HRV) such as SDNN, HF band, RMSSD, SD1, and SD2 significantly reduced. In MVZ of septic rats, many cholinergic and catecholaminergic neurons showed apoptotic, with low expressions of tyrosine hydroxylase and choline acetyltransferase. The α7nAChR agonist GTS-21 can improve these pathologies, while the α7nAChR antagonist MLA is the opposite. Our study demonstrates for the first time that cholinergic and catecholaminergic neurons in MVZ went through significant apoptosis and inactiveness in sepsis, which contributes to the inhibition of CAP and acceleration of the inflammation storm in early sepsis. Intervening with CAP has a significant effect on the activity and apoptosis of MVZ neurons while altering systemic inflammation and immunity; in addition, for the first time, we confirmed that some indicators of HRV such as SDNN, HF band, RMSSD, SD1, and SD2 can reflect the activity of CAP, but the CAP interference had little effect on these indicators.

show abstract

Section: Discussionmentioning

confidence: 99%

Exploring the Mechanism on the Medullary Visceral Zone Inhibiting the Cholinergic Anti-inflammatory Pathway Induced by Sepsis

Zhou

Zhao³

et al. 2020

Mediators of Inflammation

View full text Add to dashboard Cite

show abstract

“…Neurons from the RVM project to the locus coeruleus (LC), which innervates higher brain sites, such as the hypothalamus and PVN. Neuronal projections from the RVM and LC reach sympathetic preganglionic neurons in the spinal cord (Fernandez and Acuna-Castillo, 2012 ). Conversely, the PVN projects back to the RVM and NTS (Pavlov et al, 2003 ), completing the necessary connections for interaction between the HPA axis and autonomic (sympathetic and parasympathetic) cardiorespiratory reflex activation.…”

Section: Reflex Regulation Of Systemic Inflammation: Immune-to-brain mentioning

confidence: 99%

Neural reflex regulation of systemic inflammation: potential new targets for sepsis therapy

et al. 2014

Self Cite

View full text Add to dashboard Cite

Sepsis progresses to multiple organ dysfunction due to the uncontrolled release of inflammatory mediators, and a growing body of evidence shows that neural signals play a significant role in modulating the immune response. Thus, similar toall other physiological systems, the immune system is both connected to and regulated by the central nervous system. The efferent arc consists of the activation of the hypothalamic–pituitary–adrenal axis, sympathetic activation, the cholinergic anti-inflammatory reflex, and the local release of physiological neuromodulators. Immunosensory activity is centered on the production of pro-inflammatory cytokines, signals that are conveyed to the brain through different pathways. The activation of peripheral sensory nerves, i.e., vagal paraganglia by the vagus nerve, and carotid body (CB) chemoreceptors by the carotid/sinus nerve are broadly discussed here. Despite cytokine receptor expression in vagal afferent fibers, pro-inflammatory cytokines have no significant effect on vagus nerve activity. Thus, the CB may be the source of immunosensory inputs and incoming neural signals and, in fact, sense inflammatory mediators, playing a protective role during sepsis. Considering that CB stimulation increases sympathetic activity and adrenal glucocorticoids release, the electrical stimulation of arterial chemoreceptors may be suitable therapeutic approach for regulating systemic inflammation.

show abstract

“…TNF, IL‐6, and lipopolysaccharide (LPS) stimulate the hypothalamic‐pituitary‐adrenal (HPA) axis, resulting in increased production of cortisol that constrains immune responses to prevent excess inflammation . This stimulation of HPA hormone secretion is due, in part, to afferent vagal fiber activation of the nucleus tractus solitarius [NTS]‐to‐paraventricular nucleus [PVN] neurocircuit culminating in adrenocorticotropic hormone (ACTH) and subsequent adrenocortical secretion of cortisol (Fig.…”

Section: Introductionmentioning

confidence: 99%

Noninvasive Transcutaneous Vagus Nerve Stimulation Decreases Whole Blood Culture-Derived Cytokines and Chemokines: A Randomized, Blinded, Healthy Control Pilot Trial

Lerman¹,

Hauger

Sorkin

et al. 2016

Neuromodulation: Technology at the Neural Interface

141

117

View full text Add to dashboard Cite

Objectives: The purpose of this study was to test the transcutaneous noninvasive vagus nerve stimulator (nVNS) (gammaCoreV C ) device to determine if it modulates the peripheral immune system, as has been previously published for implanted vagus nerve stimulators. Materials and Methods:A total of 20 healthy males and females were randomized to receive either nVNS or sham stimulation (SST). All subjects underwent an initial blood draw at 8:00 AM, followed by stimulation with nVNS or SST at 8:30 AM. Stimulation was repeated at 12:00 PM and 6:00 PM. Additional blood samples were withdrawn 90 min and 24 hour after the first stimulation session. After samples were cultured using the Myriad RBM TruCulture (Austin, TX) system (WBCx), levels of cytokines and chemokines were measured by the Luminex assay and statistical analyses within and between groups were performed using the Wilcoxon Signed Ranks Test and Mann-Whitney U with the statistical program R.Results: A significant percent decrease in the levels of the cytokine interleukin [IL]-1b, tumor necrosis factor [TNF] levels, and chemokine, interleukin [IL]-8 IL-8, macrophage inflammatory protein [MIP]-1a, and monocyte chemoattractant protein [MCP]-1 levels was observed in the nVNS group non-lipopolysaccharide (LPS)-stimulated whole blood culture (n-WBCx) at the 24-hour time point (p < 0.05). In SST group, there was a significant percent increase in IL-8 at 90 min post-stimulation (p < 0.05). At 90 min, the nVNS group had a greater percent decrease in IL-8 concentration (p < 0.05) compared to SST group. The nVNS group had a greater percent decrease in cytokines (TNF, IL-1b) and chemokines (MCP-1 and IL-8) at 24 hour (p < 0.05) in comparison to SST. LPSstimulated whole blood cultures (L-WBCx) did not show a significant decrease in cytokine levels in either the nVNS or SST group across any time points. The nVNS group showed a significant percent increase in LPS-stimulated IL-10 levels at the 24-hour time point in comparison to SST.Conclusions: nVNS downregulates inflammatory cytokine release suggesting that nVNS may be an effective anti-inflammatory treatment.

show abstract

Neural Reflex Control of Inflammation During Sepsis Syndromes

Cited by 6 publications

References 128 publications

Exploring the Mechanism on the Medullary Visceral Zone Inhibiting the Cholinergic Anti-inflammatory Pathway Induced by Sepsis

Exploring the Mechanism on the Medullary Visceral Zone Inhibiting the Cholinergic Anti-inflammatory Pathway Induced by Sepsis

Neural reflex regulation of systemic inflammation: potential new targets for sepsis therapy

Noninvasive Transcutaneous Vagus Nerve Stimulation Decreases Whole Blood Culture-Derived Cytokines and Chemokines: A Randomized, Blinded, Healthy Control Pilot Trial

Contact Info

Product

Resources

About