Effect of hyperoxic and hyperbaric conditions on the adenosinergic pathway and CD26 expression in rat

Bruzzese, Laurie; Rostain, Jean-Claude; Nee, Laetitia; Condo, Jocelyne; Mottola, Giovanna; Adjriou, Nabil; Mercier, Laurence; Bergé-Lefranc, Jean-Louis; Fromonot, Julien; Kipson, Nathalie; Lucciano, Michel; Durand‐Gorde, Josée‐Martine; Jammes, Yves; Guieu, Régis; Ruf, Jean; Fenouillet, Emmanuel

doi:10.1152/japplphysiol.00223.2015

Cited by 16 publications

(28 citation statements)

References 65 publications

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“…Our results and previous studies support the fact that APL is generated in an oxygen-dependent manner (Schrader et al, 1990). Indeed, it has been reported that hypoxia induced an increase in APL (Eltzschig et al, 2006;Joulia et al, 2013) whereas hyperoxia lead to a decrease in APL (Bruzzese et al, 2015;Fromonot et al, 2016). The impact of adenosine on the hemodynamic status is well recognized and could contribute to the cardio-vascular changes observed in our healthy volunteers.…”

Section: Discussionsupporting

confidence: 91%

“…A decrease in muscle sympathetic nerve activity has been reported at rest but not during exercise (Seals et al, 1991). Recently, a decrease in adenosine plasma levels (APLs) has been reported in rats subjected to normobaric or hyperbaric hyperoxia (Bruzzese et al, 2015). Adenosine is an ATP derivative which strongly impacts heart rate and blood pressure through its G-protein coupled receptors known as A1, A2A, A2B, or A3R, depending on their pharmacological properties (Burnstock, 2017).…”

Section: Introductionmentioning

confidence: 99%

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Hyperoxia During Exercise: Impact on Adenosine Plasma Levels and Hemodynamic Data

et al. 2020

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Introduction: Adenosine is an ATP derivative that is strongly implicated in the cardiovascular adaptive response to exercise. In this study, we hypothesized that during exercise the hyperemia, commonly observed during exercise in air, was counteracted by the downregulation of the adenosinergic pathway during hyperoxic exposure.Methods: Ten healthy volunteers performed two randomized sessions including gas exposure (Medical air or Oxygen) at rest and during exercise performed at 40% of maximal intensity, according to the individual fitness of the volunteers. Investigations included the measurement of adenosine plasma level (APL) and the recording of hemodynamic data [i.e., cardiac output (CO) and systemic vascular resistances (SVR) using pulsed Doppler and echocardiography].Results: Hyperoxia significantly decreased APL (from 0.58 ± 0.06 to 0.21 ± 0.05 µmol L −1 , p < 0.001) heart rate and CO and increased SVR in healthy volunteers at rest. During exercise, an increase in APL was recorded in the two sessions when compared with measurements at rest (+0.4 ± 0.4 vs. +0.3 ± 0.2 µmol L −1 for medical air and oxygen exposures, respectively). APL was lower during the exercise performed under hyperoxia when compared with medical air exposure (0.5 ± 0.06 vs. 1.03 ± 0.2 µmol L −1 , respectively p < 0.001). This result could contribute to the hemodynamic differences between the two conditions, such as the increase in SVR and the decrease in both heart rate and CO when exercises were performed during oxygen exposure as compared to medical air.Conclusion: Hyperoxia decreased APLs in healthy volunteers at rest but did not eliminate the increase in APL and the decrease in SVR during low intensity exercise.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Hyperoxia During Exercise: Impact on Adenosine Plasma Levels and Hemodynamic Data

et al. 2020

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“…Mechanisms underlying this response may involve a down-regulation of the adenosine pathway [28] or modulation of the ROS-mediated prostaglandin and NO pathways [29] with reduced NO bioavailability [30]. In our study, hyperoxia led to an early decrease in microcirculatory vessel density and perfusion after 2 min of exposure.…”

Section: Discussionmentioning

confidence: 68%

Effects of short-term hyperoxia on erythropoietin levels and microcirculation in critically Ill patients: a prospective observational pilot study

et al. 2017

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BackgroundThe normobaric oxygen paradox states that a short exposure to normobaric hyperoxia followed by rapid return to normoxia creates a condition of ‘relative hypoxia’ which stimulates erythropoietin (EPO) production. Alterations in glutathione and reactive oxygen species (ROS) may be involved in this process. We tested the effects of short-term hyperoxia on EPO levels and the microcirculation in critically ill patients.MethodsIn this prospective, observational study, 20 hemodynamically stable, mechanically ventilated patients with inspired oxygen concentration (FiO2) ≤0.5 and PaO2/FiO2 ≥ 200 mmHg underwent a 2-hour exposure to hyperoxia (FiO2 1.0). A further 20 patients acted as controls. Serum EPO was measured at baseline, 24 h and 48 h. Serum glutathione (antioxidant) and ROS levels were assessed at baseline (t0), after 2 h of hyperoxia (t1) and 2 h after returning to their baseline FiO2 (t2). The microvascular response to hyperoxia was assessed using sublingual sidestream dark field videomicroscopy and thenar near-infrared spectroscopy with a vascular occlusion test.ResultsEPO increased within 48 h in patients exposed to hyperoxia from 16.1 [7.4–20.2] to 22.9 [14.1–37.2] IU/L (p = 0.022). Serum ROS transiently increased at t1, and glutathione increased at t2. Early reductions in microvascular density and perfusion were seen during hyperoxia (perfused small vessel density: 85% [95% confidence interval 79–90] of baseline). The response after 2 h of hyperoxia exposure was heterogeneous. Microvascular perfusion/density normalized upon returning to baseline FiO2.ConclusionsA two-hour exposure to hyperoxia in critically ill patients was associated with a slight increase in EPO levels within 48 h. Adequately controlled studies are needed to confirm the effect of short-term hyperoxia on erythropoiesis.Trial registrationClinicalTrials.gov (www.clinicaltrials.gov), NCT02481843, registered 15th June 2015, retrospectively registered

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“…A large number of human CNS disease studies have implicated adenosine 2A receptors (A 2A ), including schizophrenia [192], Pick's disease [193], MCI [194], bipolar disorder [195], and HD [196], and additionally in pre-clinical models of AD [197], addiction [198], aging [199], attention deficit hyperactivity disorder [200], epilepsy [201], hyperoxia [202], multiple sclerosis (MS) [203], PD [204], restless leg syndrome [205], and tauopathy [206], amongst others. For in-depth reviews, refer to Waarde et al [207] and Cheffer et al [208].…”

Section: Adenosine a 2amentioning

confidence: 99%

Advances in CNS PET: the state-of-the-art for new imaging targets for pathophysiology and drug development

McCluskey

Plisson

Rabiner

et al. 2019

Eur J Nucl Med Mol Imaging

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Purpose A limit on developing new treatments for a number of central nervous system (CNS) disorders has been the inadequate understanding of the in vivo pathophysiology underlying neurological and psychiatric disorders and the lack of in vivo tools to determine brain penetrance, target engagement, and relevant molecular activity of novel drugs. Molecular neuroimaging provides the tools to address this. This article aims to provide a state-of-the-art review of new PET tracers for CNS targets, focusing on developments in the last 5 years for targets recently available for inhuman imaging. Methods We provide an overview of the criteria used to evaluate PET tracers. We then used the National Institute of Mental Health Research Priorities list to identify the key CNS targets. We conducted a PubMed search (search period 1st of January 2013 to 31st of December 2018), which yielded 40 new PET tracers across 16 CNS targets which met our selectivity criteria. For each tracer, we summarised the evidence of its properties and potential for use in studies of CNS pathophysiology and drug evaluation, including its target selectivity and affinity, inter and intra-subject variability, and pharmacokinetic parameters. We also consider its potential limitations and missing characterisation data, but not specific applications in drug development. Where multiple tracers were present for a target, we provide a comparison of their properties. Results and conclusions Our review shows that multiple new tracers have been developed for proteinopathy targets, particularly tau, as well as the purinoceptor P2X7, phosphodiesterase enzyme PDE10A, and synaptic vesicle glycoprotein 2A (SV2A), amongst others. Some of the most promising of these include 18 F-MK-6240 for tau imaging, 11 C-UCB-J for imaging SV2A, 11 C-CURB and 11 C-MK-3168 for characterisation of fatty acid amide hydrolase, 18 F-FIMX for metabotropic glutamate receptor 1, and 18 F-MNI-444 for imaging adenosine 2A. Our review also identifies recurrent issues within the field. Many of the tracers discussed lack in vivo blocking data, reducing confidence in selectivity. Additionally, late-stage identification of substantial off-target sites for multiple tracers highlights incomplete preclinical characterisation prior to translation, as well as human disease state studies carried out without confirmation of test-retest reproducibility.

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Effect of hyperoxic and hyperbaric conditions on the adenosinergic pathway and CD26 expression in rat

Cited by 16 publications

References 65 publications

Hyperoxia During Exercise: Impact on Adenosine Plasma Levels and Hemodynamic Data

Hyperoxia During Exercise: Impact on Adenosine Plasma Levels and Hemodynamic Data

Effects of short-term hyperoxia on erythropoietin levels and microcirculation in critically Ill patients: a prospective observational pilot study

Advances in CNS PET: the state-of-the-art for new imaging targets for pathophysiology and drug development

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