Peripheral and central compensatory mechanisms for impaired vagus nerve function during peripheral immune activation

Anna Kobrzycka , Pawel Napora , Brandon L. Pearson , Krystyna Pierzchała-Koziec , Rafał Szewczyk , Marek Wieczorek


Background. Determining the etiology and possible treatment strategies for numerous diseases requires a comprehensive understanding of compensatory mechanisms in physiological systems. The vagus nerve acts as a key interface between the brain and the peripheral internal organs. We set out to identify mechanisms compensating for a lack of neuronal communication between the immune and the central nervous system (CNS) during infection. Methods. We assessed biochemical and central neurotransmitter changes resulting from subdiaphragmatic vagotomy and whether they are modulated by intraperitoneal infection. We performed a series of subdiaphragmatic vagotomy or sham operations on male Wistar rats. Next, after full, 30-day recovery period, they were randomly assigned to receive an injection of Escherichia coli lipopolysaccharide or saline. Two hours later, animal were euthanized and we measured the plasma concentration of prostaglandin E2 (with HPLC-MS), interleukin-6 (ELISA), and corticosterone (RIA). We also had measured the concentration of monoaminergic neurotransmitters and their metabolites in the amygdala, brainstem, hippocampus, hypothalamus, motor cortex, periaqueductal gray, and prefrontal medial cortex using RP-HPLC-ED. A subset of the animals was evaluated in the elevated plus maze test immediately before euthanization. Results. The lack of immunosensory signaling of the vagus nerve stimulated increased activity of discrete inflammatory marker signals, which we confirmed by quantifying biochemical changes in blood plasma. Behavioral results, although preliminary, support the observed biochemical alterations. Many of the neurotransmitter changes observed after vagotomy indicated that the vagus nerve influences the activity of many brain areas involved in control of immune response and sickness behavior. Our studies show that these changes are largely eliminated during experimental infection. Conclusions. Our results suggest that in vagotomized animals with blocked CNS, communication may transmit via a pathway independent of the vagus nerve to permit restoration of CNS activity for peripheral inflammation control.
Author Anna Kobrzycka
Anna Kobrzycka,,
, Pawel Napora
Pawel Napora,,
, Brandon L. Pearson
Brandon L. Pearson,,
, Krystyna Pierzchała-Koziec (FoAS / DoAPaE)
Krystyna Pierzchała-Koziec,,
- Department of Animal Physiology and Endocrinology
, Rafał Szewczyk
Rafał Szewczyk,,
, Marek Wieczorek
Marek Wieczorek,,
Journal seriesJournal of Neuroinflammation, ISSN 1742-2094, (N/A 100 pkt)
Issue year2019
Publication size in sheets0.85
Article number150
Keywords in EnglishVagus nerve, Vagotomy, Prostaglandin E2, PGE2, Compensatory mechanisms, CNS communication, LPS, Elevated plus maze test, Sickness behavior
ASJC Classification2403 Immunology; 2800 General Neuroscience; 2804 Cellular and Molecular Neuroscience; 2808 Neurology
Languageen angielski
LicenseJournal (articles only); author's original; Uznanie Autorstwa (CC-BY); after publication
Score (nominal)100
Score sourcejournalList
Publication indicators WoS Citations = 0; Scopus SNIP (Source Normalised Impact per Paper): 2018 = 1.323; WoS Impact Factor: 2018 = 5.7 (2) - 2018=6.016 (5)
Citation count*
Additional fields
FinansowanieThis work was supported by the Polish National Science Center (NCN, UMO 2012/07/B/NZ4/00205).
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