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Translational 3D-Cell Culture Model to Assess Hyperoxia Effects on Human Neonatal Airway Epithelial Cells

The preterm neonatal airway epithelium is constantly exposed to environmental stressors. One of these stressors in neonates with lung disease includes ...

University of Oklahoma Health Sciences Center

Longer term respiratory morbidity is a frequent concern for former preterm infants. Increased airway reactivity and wheezing disorders are extremely common in this population, both in infants who meet diagnostic criteria for bronchopulmonary dysplasia [BPD], and in the absence of this diagnosis. It is, therefore, imperative to gain a better understanding of normal and abnormal postnatal development of the immature airway. Airway hyperreactivity may be secondary to abnormal bronchoalveolar attachments in the face of parenchymal lung injury, or secondary to an imbalance between constrictor and dilator neural pathways. Finally, the airway itself may undergo functional and/or structural changes, including increased airway smooth muscle mass, and changes in airway extracellular matrix which may, in turn, modulate downstream signaling pathways to hyperoxia or pressure exposed vulnerable airways.

Vulnerability of the developing airway.

Respiratory management of the extremely low birth weight (ELBW) newborn has evolved over time. Although non-invasive ventilation is being increasingly used for respiratory support in these ELBW infants, invasive ventilation still remains the primary mode in this population. Current ventilators are microprocessor driven and have revolutionized the respiratory support for these neonates synchronizing the baby's breath to ventilator breaths. High frequency ventilators with the delivery of tidal volumes less than the dead space have been introduced to minimize barotrauma and chronic lung disease. Despite these advances, the incidence of chronic lung disease has not decreased. There is still controversy regarding which mode is ideal as the primary mode of ventilation in ELBW infants. The most common modes seem to be pressure targeted conventional ventilation, volume targeted conventional ventilation and high frequency ventilation which includes high frequency oscillatory ventilation, high frequency jet ventilation and high frequency flow interrupter. In recent years, several randomized controlled trials and meta-analyses have compared volume vs. pressure targeted ventilation and high frequency ventilation. While volume targeted ventilation and high frequency ventilation does show promise, substantial practice variability among different centers persists. In this review, we weighed the evidence for each mode and evaluated which modes show promise as the primary support of ventilation in ELBW babies.

Volume Targeted Ventilation and High Frequency Ventilation as the Primary Modes of Respiratory Support for ELBW Babies: What Does the Evidence Say?

There is a widespread shortage of physicians worldwide, especially in rural areas. This shortage is more prevalent when it comes to subspecialty care, even in developed countries. One way to provide access to specialty care is using technology via telemedicine. Telemedicine has evolved over the last two decades, and its use is becoming widespread in developed countries. However, its use in the neonatal population is still limited and practiced only in some centers. It is now apparent that telemedicine can be successfully used in the neonatal population for screening premature infants for retinopathy of prematurity, congenital heart disease, bedside clinical rounds, neonatal resuscitation with the support of a tertiary care hospital, and family support. This avoids unnecessary transfer and appears to provide the same quality of care that the baby would have received at the tertiary care facility. This approach also improves family satisfaction, as the baby and the mother are kept together, and reduces the cost of care. This review focuses on the use of telemedicine in neonatal care, concentrating on the main areas where telemedicine has been shown to be successful and effective, including the status of telemedicine in China.

Scope of telemedicine in neonatology.

Tele-Echocardiography for Congenital Heart Disease Screening in a Level II Neonatal Intensive Care Unit with Hybrid Telemedicine System.

Reactive oxygen species (ROS) have been the focus of redox research in the realm of oxidative neonatal respiratory diseases such as bronchopulmonary dysplasia (BPD). Over the years, nitric oxide (NO) and carbon monoxide (CO) have been identified as important gaseous signaling molecules involved in modulating the redox homeostasis in the developing lung. While animal data targeting aspects of these redox pathways have been promising in treating and/or preventing experimental models of neonatal lung disease, none are particularly effective in human neonatal clinical trials. In recent years, hydrogen sulfide (HS) has emerged as a novel gasotransmitter involved in a magnitude of cellular signaling pathways and functions. The importance of HS signaling may lie in the fact that early life-forms evolved in a nearly anoxic, sulfur-rich environment and were dependent on HS for energy. Recent studies have demonstrated an important role of HS and its synthesizing enzymes in lung development, which normally takes place in a relatively hypoxic intrauterine environment. In this review, we look at clues from evolution and explore the important role that the HS signaling pathway may play in oxidative neonatal respiratory diseases and discuss future opportunities to explore this phenomenon in the context of neonatal chronic lung disease.

Hydrogen Sulfide-Clues from Evolution and Implication for Neonatal Respiratory Diseases.

Astrocytic dysfunction is central to age-related neurodegenerative diseases. However, the mechanisms leading to astrocytic dysfunction are not well understood. We identify that among the diverse cellular constituents of the brain, murine and human astrocytes are enriched in the expression of CBS. Depleting CBS in astrocytes causes mitochondrial dysfunction, increases the production of reactive oxygen species (ROS) and decreases cellular bioenergetics that can be partially rescued by exogenous HS supplementation or by re-expressing CBS. Conversely, the CBS/HS axis, associated protein persulfidation and proliferation are decreased in astrocytes upon oxidative stress which can be rescued by exogenous HS supplementation. Here we reveal that in the aging brain, the CBS/HS axis is downregulated leading to decreased protein persulfidation, together augmenting oxidative stress. Our findings uncover an important protective role of the CBS/HS axis in astrocytes that may be disrupted in the aged brain.

Abhrajit Ganguly

Department of Pediatrics,
Section of Neonatal-Perinatal Medicine,
Center for Pregnancy and Newborn Health,
Department of Pediatrics, Section of Neonatal-Perinatal Medicine, Center for Pregnancy and Newborn Health

University of Oklahoma Health Sciences Center

Translational 3D-Cell Culture Model to Assess Hyperoxia Effects on Human Neonatal Airway Epithelial Cells

Abhrajit Ganguly

Department of Pediatrics,Section of Neonatal-Perinatal Medicine,Center for Pregnancy and Newborn Health,Department of Pediatrics, Section of Neonatal-Perinatal Medicine, Center for Pregnancy and Newborn Health

University of Oklahoma Health Sciences Center

Translational 3D-Cell Culture Model to Assess Hyperoxia Effects on Human Neonatal Airway Epithelial Cells

Department of Pediatrics,
Section of Neonatal-Perinatal Medicine,
Center for Pregnancy and Newborn Health,
Department of Pediatrics, Section of Neonatal-Perinatal Medicine, Center for Pregnancy and Newborn Health