scholarly journals Umbilical cord occlusions in near-term ovine fetus induce increased beat-to-beat heart rate variability correlating to decreases in neuroinflammation: a case for the afferent cholinergic anti-inflammatory pathway?

2015 ◽  
Author(s):  
Martin G Frasch ◽  
Mark Szynkaruk ◽  
Andrew P Prout ◽  
Karen Nygard ◽  
Ruud Veldhuizen ◽  
...  
Keyword(s):  
Heart Rate ◽  
Heart Rate Variability ◽  
Vagus Nerve ◽  
Fetal Brain ◽  
In Utero ◽  
Inflammatory Pathway ◽  
Anti Inflammatory ◽  
Near Term ◽  
Ovine Fetal

Neuroinflammation in utero may contribute to brain injury resulting in life long neurological disabilities. The pivotal role of the efferent cholinergic anti-inflammatory pathway (CAP) in controlling inflammation has been described in adults, but its importance in the fetus is unknown. Moreover, it is unknown whether CAP may also exert anti-inflammatory effects on the brain via CAP's afferent component of the vagus nerve. Based on multiple clinical studies in adults and our own work in fetal autonomic nervous system, we gauged the degree of CAP activity in vivo using heart rate variability measures reflecting fluctuations in vagus nerve activity. Measuring microglial activation in the ovine fetal brain near-term, we show in vivo that afferent fetal CAP may translate increased vagal cholinergic signaling into suppression of cerebral inflammation in response to near-term hypoxic acidemia as might occur during labour. Our findings suggest a new control mechanism of fetal neuroinflammation via the vagus nerve, providing novel possibilities for its non-invasive monitoring in utero and for targeted treatment.

scholarly journals Heart rate variability predicts levels of inflammatory markers: Evidence for the vagal anti-inflammatory pathway

2015 ◽  
Vol 49 ◽  
pp. 94-100 ◽  
Author(s):  
Timothy M. Cooper ◽  
Paula S. McKinley ◽  
Teresa E. Seeman ◽  
Tse-Hwei Choo ◽  
Seonjoo Lee ◽  
...  
Keyword(s):  
Heart Rate ◽  
Heart Rate Variability ◽  
Inflammatory Markers ◽  
Inflammatory Pathway ◽  
Anti Inflammatory

Glutamate Release from the Ovine Fetal Brain during Maternal Hemorrhage 

1995 ◽  
Vol 82 (2) ◽  
pp. 521-530 ◽  
Author(s):  
Donald H. Penning ◽  
David H. Chestnut ◽  
Franklin Dexter ◽  
James Hrdy ◽  
Dan Poduska ◽  
...  
Keyword(s):  
Parietal Cortex ◽  
Glutamate Release ◽  
Recovery Period ◽  
Fetal Brain ◽  
In Utero ◽  
Extracellular Glutamate ◽  
Microdialysis Probe ◽  
Fetal Sheep ◽  
Near Term ◽  
Ovine Fetal

Background Glutamate has been implicated in the pathophysiology of neuronal injury associated with cerebral hypoxia-ischemia. A model using chronic in utero microdialysis was developed to sample the extracellular space of the fetal brain. Using this model, we tested the hypothesis that glutamate efflux from the parasagittal parietal cortex of near-term fetuses would increase during maternal hemorrhage. Methods Twelve near-term fetal sheep were instrumented with vascular catheters, and a microdialysis probe(s) was implanted into the parasagittal parietal cortex. After a 3-day recovery period, the animals were subjected to maternal hemorrhage until either the fetal pH was < 7.00 or the fetus died. The extracellular glutamate concentration in the collected dialysate was determined by high pressure liquid chromatography (HPLC). Results Maternal hemorrhage resulted in an 80-90% decrease in uterine blood flow, a decrease fetal po2, and a mixed metabolic and respiratory fetal acidosis. There were two groups of fetuses, survivors (n = 5) and nonsurvivors (n = 7). The nonsurvivor group showed a large increase (10-30-fold) in peak glutamate release (P = 0.0015). Survivors demonstrated a small (threefold) increase that was not statistically significant (P = 0.065), unless one animal with very low probe recovery was excluded (P = 0.0048). Conclusions Extracellular glutamate release from the fetal brain can occur during maternal hemorrhage with fetal acidemia. The pathophysiologic role (if any) of glutamate release in the survivors remains to be elucidated. Our results are consistent with the hypothesis that in utero release of glutamate occurs during periods of fetal asphyxia. This experimental preparation of chronic fetal brain microdialysis can be used to monitor the brain extracellular concentration of any dialyzable substance in response to stress, including maternal hemorrhage.

Neuropathology of the near-term and midgestation ovine fetal brain after sustained in utero hypoxemia

1994 ◽  
Vol 170 (5) ◽  
pp. 1425-1432 ◽  
Author(s):  
Donald H. Penning ◽  
Marjorie R. Grafe ◽  
Robert Hammond ◽  
Yoshio Matsuda ◽  
John Patrick ◽  
...  
Keyword(s):  
Fetal Brain ◽  
In Utero ◽  
Near Term ◽  
Ovine Fetal

scholarly journals Neural signature of cerebral activity of the fetal cholinergic anti‐inflammatory pathway derived from heart rate variability

2013 ◽  
Vol 27 (S1) ◽  
Author(s):  
Lucien Daniel Durosier ◽  
Alex Xu ◽  
Brad Matushewski ◽  
Mingju Cao ◽  
Christophe Herry ◽  
...  
Keyword(s):  
Heart Rate ◽  
Heart Rate Variability ◽  
Inflammatory Pathway ◽  
Cerebral Activity ◽  
Neural Signature ◽  
Anti Inflammatory

scholarly journals Activation of the Cholinergic Anti-Inflammatory Pathway as a Novel Therapeutic Strategy for COVID-19

2021 ◽  
Vol 11 ◽  
Author(s):  
Zhen Qin ◽  
Kefa Xiang ◽  
Ding-Feng Su ◽  
Yang Sun ◽  
Xia Liu
Keyword(s):  
Vagus Nerve ◽  
Therapeutic Strategy ◽  
Inflammatory Pathway ◽  
Non Invasive ◽  
Anti Inflammatory ◽  
Approved Drugs ◽  
And Control ◽  
Anti Inflammation

The outbreak of coronavirus disease 2019 (COVID-19) underlined the urgent need for alleviating cytokine storm. We propose here that activating the cholinergic anti-inflammatory pathway (CAP) is a potential therapeutic strategy. However, there is currently no approved drugs targeting the regulatory pathway. It is evident that nicotine, anisodamine and some herb medicine, activate the CAP and exert anti-inflammation action in vitro and in vivo. As the vagus nerve affects both inflammation and specific immune response, we propose that vagus nerve stimulation by invasive or non-invasive devices and acupuncture at ST36, PC6, or GV20, are also feasible approaches to activate the CAP and control COVID-19. It is worth to investigate the efficacy and safety of the strategy in patients with COVID-19.

Neuropathology of the near-term and midgestation ovine fetal brain after sustained in utero hypoxemia

1994 ◽  
Vol 170 (5) ◽  
pp. 1425-1432 ◽  
Author(s):  
Donald H. Penning ◽  
Marjorie R. Grafe ◽  
Robert Hammond ◽  
Yoshio Matsuda ◽  
John Patrick ◽  
...  
Keyword(s):  
Fetal Brain ◽  
In Utero ◽  
Near Term ◽  
Ovine Fetal
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