Compensatory ventilatory responses to increased inspiratory loading are essential for adequate breathing regulation in a number of pulmonary diseases; however, the human brain sites mediating such responses are unknown. Midsagittal and axial images were acquired in 11 healthy volunteers during unloaded and loaded (30 cmH2O; 1 cmH2O = 98 Pa) inspiratory breathing, by using functional magnetic resonance imaging (fMRI) strategies (1.5-tesla MR; repetition time, 72 msec; echo time, 45 msec; flip angle, 30 degrees; field of view, 26 cm; slice thickness, 5 mm; number of excitations, 1; matrix, 128 x 256). Digital image subtractions and region of interest analyses revealed significantly increased fMRI signal intensity in discrete areas of the ventral and dorsal pons, interpeduncular nucleus, basal forebrain, putamen, and cerebellar regions. Upon load withdrawal, certain regions displayed a rapid fMRI signal off-transient, while in others, a slower fMRI signal decay emerged. Sustained loading elicited slow decreases in fMRI signal across activated regions, while second application of an identical load resulted in smaller signal increases compared to initial signal responses (P < 0.001). A moderate inspiratory load is associated with consistent regional activation of discrete brain locations; certain of these regions have been implicated in mediation of loaded breathing in animal models. We speculate that temporal changes in fMRI signal may indicate respiratory after-discharge and/or habituation phenomena.
Obstructive sleep apnea (OSA) in children has emerged not only as a relatively prevalent condition but also as a disease that imposes a large array of morbidities, some of which may have long-term implications, well into adulthood. The major consequences of pediatric OSA involve neurobehavioral, cardiovascular, and endocrine and metabolic systems. The underlying pathophysiological mechanisms of OSA-induced end-organ injury are now being unraveled, and clearly involve oxidative and inflammatory pathways. However, the roles of individual susceptibility (as dictated by single-nucleotide polymorphisms), and of environmental and lifestyle conditions (such as diet, physical, and intellectual activity), may account for a substantial component of the variance in phenotype. Moreover, the clinical prototypic pediatric patient of the early 1990s has been insidiously replaced by a different phenotypic presentation that strikingly resembles that of adults afflicted by the disease. As such, analogous to diabetes, the t...
Machine-learning approaches have enabled promising results in efforts to simplify the diagnosis of pediatric obstructive sleep apnea (OSA). A comprehensive review and analysis of such studies increase the confidence level of practitioners and healthcare providers in the implementation of these methodologies in clinical practice.
We tested the hypothesis that oleic acid-induced acute lung injury activates pulmonary nociceptors, that is, C fibre receptors (CFRs) and high-threshold Adelta fibre receptors (HTARs). Single-unit activity was recorded in the cervical vagus nerve and assessed before and after injecting oleic acid (75 microl kg(-1) i.v.) into anaesthetized, open-chest, mechanically ventilated rabbits. Unit activities increased within seconds and peaked within a few minutes (from 0.3 +/- 0.1 to 1.4 +/- 0.9 impulses s(-1) for CFRs and from 0.5 +/- 0.1 to 1.7 +/- 0.3 impulses s(-1) for HTARs, both n = 8 and P < 0.05). These activities were sustained while pulmonary oedema developed and dynamic lung compliance decreased over the 90 min observation period. Activities in slowly adapting receptors and rapidly adapting receptors were also increased; however, their responsiveness to airway pressure stimulation decreased progressively. We conclude that pulmonary nociceptors are stimulated during acute lung injury. The dual nociceptor system, consisting of both non-myelinated CFRs and myelinated HTARs, may play an important role in the pathophysiological process of acute lung injury-induced respiratory responses.
Intermittent hypoxia (IH) is a hallmark of obstructive sleep apnea (OSA) and induces metabolic dysfunction manifesting as inflammation, increased lipolysis and insulin resistance in visceral white adipose tissues (vWAT). However, the cell types and their corresponding transcriptional pathways underlying these functional perturbations are unknown. Here, we applied single nucleus RNA sequencing (snRNA-seq) coupled with aggregate RNA-seq methods to evaluate the cellular heterogeneity in vWAT following IH exposures mimicking OSA. C57BL/6 male mice were exposed to IH and room air (RA) for 6 weeks, and nuclei from vWAT were isolated and processed for snRNA-seq followed by differential expressed gene (DEGs) analyses by cell type, along with gene ontology and canonical pathways enrichment tests of significance. IH induced significant transcriptional changes compared to RA across 14 different cell types identified in vWAT. We identified cell-specific signature markers, transcriptional networks, metabolic signaling pathways, and cellular subpopulation enrichment in vWAT. Globally, we also identify 298 common regulated genes across multiple cellular types that are associated with metabolic pathways. Deconvolution of cell types in vWAT using global RNA-seq revealed that distinct adipocytes appear to be differentially implicated in key aspects of metabolic dysfunction. Thus, the heterogeneity of vWAT and its response to IH at the cellular level provides important insights into the metabolic morbidity of OSA and may possibly translate into therapeutic targets.
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