scholarly journals Raphe gene expression changes implicate immune-related functions in ventilatory plasticity following carotid body denervation in rats

2017 ◽  
Vol 287 ◽  
pp. 102-112 ◽  
Author(s):  
Gary C. Mouradian ◽  
Pengyuan Liu ◽  
Matthew R. Hodges
2020 ◽  
Vol 318 (5) ◽  
pp. H1325-H1336
Author(s):  
Jaime Eugenín ◽  
Carolina Larraín ◽  
Patricio Zapata

Unilateral carotid body denervation has been proposed as treatment for sympathetic hyperactivity-related human disorders. Its therapeutic effectiveness for maintaining a persistent decrease in the sympathetic outflow activity will depend on the absence of compensatory chemoreflex plasticity in the remnant carotid and aortic afferents. Here, we suggest that the integrity of central afferents after carotid body denervation is essential to prevent the emergence of plastic functional changes on the contralateral “intact” carotid nerve.


2010 ◽  
Vol 113 (6) ◽  
pp. 1270-1279 ◽  
Author(s):  
Malin Jonsson Fagerlund ◽  
Jessica Kåhlin ◽  
Anette Ebberyd ◽  
Gunnar Schulte ◽  
Souren Mkrtchian ◽  
...  

Background Hypoxia is a common cause of adverse events in the postoperative period, where respiratory depression due to residual effects of drugs used in anesthesia is an important underlying factor. General anesthetics and neuromuscular blocking agents reduce the human ventilatory response to hypoxia. Although the carotid body (CB) is the major oxygen sensor in humans, critical oxygen sensing and signaling pathways have been investigated only in animals so far. Thus, the aim of this study was to characterize the expression of key genes and localization of their products involved in the human oxygen sensing and signaling pathways with a focus on receptor systems and ion channels of relevance in anesthesia. Methods Six CBs were removed unilaterally from patients undergoing radical neck dissection. The gene expression and cell-specific protein localization in the CBs were investigated with DNA microarrays, real-time polymerase chain reaction, and immunohistochemistry. Results We found gene expression of the oxygen-sensing pathway, heme oxygenase 2, and the K channels TASK (TWIK-related acid sensitive K channel)-1 and BK (large-conductance potassium channel). In addition, we show the expression of critical receptor subunits such as γ-aminobutyric acid A (α2, β3, and γ2), nicotinic acetylcholine receptors (α3, α7, and β2), purinoceptors (A2A and P2X2), and the dopamine D2 receptor. Conclusions In unique samples of the human CB, we here demonstrate presence of critical proteins in the oxygen-sensing and signaling cascade. Our findings demonstrate similarities to, but also important differences from, established animal models. In addition, our work establishes an essential platform for studying the interaction between anesthetic drugs and human CB chemoreception.


2017 ◽  
Vol 30 (8) ◽  
pp. 791-798 ◽  
Author(s):  
Kana Fujii ◽  
Keita Saku ◽  
Takuya Kishi ◽  
Yasuhiro Oga ◽  
Takeshi Tohyama ◽  
...  

1981 ◽  
Vol 51 (1) ◽  
pp. 40-45 ◽  
Author(s):  
G. Bowes ◽  
E. R. Townsend ◽  
L. F. Kozar ◽  
S. M. Bromley ◽  
E. A. Phillipson

We studied the arousal and ventilatory responses to hypoxia during sleep in three trained dogs, before and 1–4 wk after carotid body denervation (CBD). During the studies the dogs breathed through a cuffed endotracheal tube inserted via a chronic tracheostomy. Eucapnic progressive hypoxia was induced by a rebreathing technique, and arterial O2 saturation (Sao2) was measured with an ear oximeter. Sleep stage was determined by electroencephalographic and behavioral criteria. Following CBD, all dogs exhibited hypoventilation under resting conditions; hypoxic ventilatory responses during wakefulness, slow-wave sleep (SWS), and rapid-eye-movement (REM) sleep were less than 10% of control. Prior to CBD, hypoxic arousal occurred at Sao2 of 83.2 +/- 4.6% (mean +/- Se) during SWS and 70.6 +/-2.2% in REM sleep. Following CBD, arousal failed to occur during progressive desaturation to 60% in SWS and 50% in REM sleep, at which levels hypoxia was arbitrarily terminated. In a few studies following CBD where rebreathing was allowed to continue, the dogs occasionally failed to arouse at all and require active resuscitation. The results indicate a critical role for the carotid chemoreceptors in mediating the arousal response to hypoxia.


2012 ◽  
Vol 112 (3) ◽  
pp. 490-500 ◽  
Author(s):  
Eric W. Kostuk ◽  
Alexander Balbir ◽  
Koichi Fujii ◽  
Akiko Fujioka ◽  
Luis E. Pichard ◽  
...  

We have previously shown that the adult DBA/2J and A/J strains of mice differ in carotid body volume and morphology. The question has arisen whether these differences develop during the prenatal or postnatal period. Investigating morphological development of the carotid body and contributing genes in these mice can provide further understanding of the appropriate formation of the carotid body. We examined the carotid body of these mice from 1 day to 4 wk old for differences in volume, morphology, and gene expression of Gdnf family, Dlx2, Msx2, and Phox2b. The two strains showed divergent morphology starting at 1 wk old. The volume of the carotid body increased from 1 wk up to 2 wk old to the level of 4 wk old in the DBA/2J mice but not in the A/J mice. This corresponds with immunoreactivity of LC3, an autophagy marker, in A/J tissues at 10 days and 2 wk. The differences in gene expression were examined at 1 wk, 10 days, and 2 wk old, because divergent growth occurred during this period. The DBA/2J's carotid body at 1 wk old showed a greater expression of Msx2 than the A/J's carotid body. No other candidate genes showed consistent differences between the ages and strains. The difference was not seen in sympathetic cervical ganglia of 1 wk old, suggesting that the difference is carotid body specific. The current study indicates the critical postnatal period for developing distinctive morphology of the carotid body in these mice. Further studies are required to further elucidate a role of Msx2 and other uninvestigated genes.


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