Bilirubin Exerts Protective Effects on Alveolar Type II Pneumocytes in an In Vitro Model of Oxidative Stress.

Newborn infants face a rapid surge of oxygen and a more protracted rise of unconjugated bilirubin after birth. Bilirubin has a strong antioxidant capacity by scavenging free radicals, but it also exerts direct toxicity. This study investigates whether cultured rat alveolar epithelial cells type II (AEC II) react differently to bilirubin under different oxygen concentrations.

Oxygen and HIF1α-dependent SDF1 expression in primary astrocytes.

In the naturally hypoxic in utero fetal environment of preterm infants, oxygen and oxygen-sensitive signaling pathways play an important role in brain development, with hypoxia-inducible factor-1α (HIF1α) being an important regulator. Early exposure to nonphysiological high oxygen concentrations by birth in room can induce HIF1α degradation and may affect neuronal and glial development. This involves the dysregulation of astroglial maturation and function, which in turn might contribute to oxygen-induced brain injury.

Cardioprotective Effects of Dexmedetomidine in an Oxidative-Stress In Vitro Model of Neonatal Rat Cardiomyocytes.

Preterm birth is a risk factor for cardiometabolic disease. The preterm heart before terminal differentiation is in a phase that is crucial for the number and structure of cardiomyocytes in further development, with adverse effects of hypoxic and hyperoxic events. Pharmacological intervention could attenuate the negative effects of oxygen.

Dexmedetomidine Protects Cerebellar Neurons against Hyperoxia-Induced Oxidative Stress and Apoptosis in the Juvenile Rat.

The risk of oxidative stress is unavoidable in preterm infants and increases the risk of neonatal morbidities. Premature infants often require sedation and analgesia, and the commonly used opioids and benzodiazepines are associated with adverse effects. Impairment of cerebellar functions during cognitive development could be a crucial factor in neurodevelopmental disorders of prematurity.

Protective Effect of Dexmedetomidine against Hyperoxia-Damaged Cerebellar Neurodevelopment in the Juvenile Rat.

Impaired cerebellar development of premature infants and the associated impairment of cerebellar functions in cognitive development could be crucial factors for neurodevelopmental disorders. Anesthetic- and hyperoxia-induced neurotoxicity of the immature brain can lead to learning and behavioral disorders. Dexmedetomidine (DEX), which is associated with neuroprotective properties, is increasingly being studied for off-label use in the NICU.

Protective Effects of Early Caffeine Administration in Hyperoxia-Induced Neurotoxicity in the Juvenile Rat.

High-risk preterm infants are affected by a higher incidence of cognitive developmental deficits due to the unavoidable risk factor of oxygen toxicity. Caffeine is known to have a protective effect in preventing associated with improved neurologic outcomes, although very early initiation of therapy is controversial. In this study, we used newborn rats in an oxygen injury model to test the hypothesis that near-birth caffeine administration modulates neuronal maturation and differentiation in the hippocampus of the developing brain.

The Conflicting Role of Caffeine Supplementation on Hyperoxia-Induced Injury on the Cerebellar Granular Cell Neurogenesis of Newborn Rats.

Preterm birth disrupts cerebellar development, which may be mediated by systemic oxidative stress that damages neuronal developmental stages. Impaired cerebellar neurogenesis affects several downstream targets important for cognition, emotion, and speech. In this study, we demonstrate that oxidative stress induced with high oxygen (80%) for three or five postnatal days (P3/P5) could significantly damage neurogenesis and proliferative capacity of granular cell precursor and Purkinje cells in rat pups.

Neonatal Oxidative Stress Impairs Cortical Synapse Formation and GABA Homeostasis in Parvalbumin-Expressing Interneurons.

Neonatal brain injury is often caused by preterm birth. Brain development is vulnerable to increased environmental stress, including oxidative stress challenges. Due to a premature change of the fetal living environment from low oxygen into postnatal high-oxygen room air conditions , the immature preterm brain is exposed to a relative hyperoxia, which can induce oxidative stress and impair neuronal cell development.

Perinatal Hyperoxia and Developmental Consequences on the Lung-Brain Axis.

Approximately 11.1% of all newborns worldwide are born preterm. Improved neonatal intensive care significantly increased survival rates over the last decades but failed to reduce the risk for the development of chronic lung disease (i.

Adaptation of the Oxygen Sensing System during Lung Development.

During gestation, the most drastic change in oxygen supply occurs with the onset of ventilation after birth. As the too early exposure of premature infants to high arterial oxygen pressure leads to characteristic diseases, we studied the adaptation of the oxygen sensing system and its targets, the hypoxia-inducible factor- (HIF-) regulated genes (HRGs) in the developing lung. We draw a detailed picture of the oxygen sensing system by integrating information from qPCR, immunoblotting, hybridization, and single-cell RNA sequencing data in and models.

Paracetamol (Acetaminophen) and the Developing Brain.

Paracetamol is commonly used to treat fever and pain in pregnant women, but there are growing concerns that this may cause attention deficit hyperactivity disorder and autism spectrum disorder in the offspring. A growing number of epidemiological studies suggests that relative risks for these disorders increase by an average of about 25% following intrauterine paracetamol exposure. The data analyzed point to a dose-effect relationship but cannot fully account for unmeasured confounders, notably indication and genetic transmission.

Postnatal myelination of the immature rat cingulum is regulated by GABA receptor activity.

Myelination of axons in the neonatal brain is a highly complex process primarily achieved by oligodendroglial cells (OLs). OLs express receptors for γ-aminobutyric acid (GABA) which is released from cortical interneurons on a basal level, while glial cells can be a source of GABA, too. We investigated GABA-induced oligodendroglial maturation, proliferation, apoptosis, and myelin production after pharmacological inhibition of GABA and GABA in the neonatal rat brain.

Reduction of cortical parvalbumin-expressing GABAergic interneurons in a rodent hyperoxia model of preterm birth brain injury with deficits in social behavior and cognition.

The inhibitory GABAergic system in the brain is involved in the etiology of various psychiatric problems, including autism spectrum disorders (ASD), attention deficit hyperactivity disorder (ADHD) and others. These disorders are influenced not only by genetic but also by environmental factors, such as preterm birth, although the underlying mechanisms are not known. In a translational hyperoxia model, exposing mice pups at P5 to 80% oxygen for 48 h to mimic a steep rise of oxygen exposure caused by preterm birth from in utero into room air, we documented a persistent reduction of cortical mature parvalbumin-expressing interneurons until adulthood.

GABA Receptor-Mediated Impairment of Intermediate Progenitor Maturation During Postnatal Hippocampal Neurogenesis of Newborn Rats.

The neurotransmitter GABA and its receptors assume essential functions during fetal and postnatal brain development. The last trimester of a human pregnancy and early postnatal life involves a vulnerable period of brain development. In the second half of gestation, there is a developmental shift from depolarizing to hyperpolarizing in the GABAergic system, which might be disturbed by preterm birth.

Dexmedetomidine Restores Autophagic Flux, Modulates Associated microRNAs and the Cholinergic Anti-inflammatory Pathway upon LPS-Treatment in Rats.

Infections and perioperative stress can lead to neuroinflammation, which in turn is linked to cognitive impairments such as postoperative delirium or postoperative cognitive dysfunctions. The α2-adrenoceptor agonist dexmedetomidine (DEX) prevents cognitive impairments and has organo-protective and anti-inflammatory properties. Macroautophagy (autophagy) regulates many biological processes, but its role in DEX-mediated anti-inflammation and the underlying mechanism of DEX remains largely unclear.

P38MAPK inhibition in aged astrocytes decreases reactive astrocytes, inflammation and increases nutritive capacity after oxygen-glucose deprivation.

Proper astroglial functioning is essential for the development and survival of neurons and oligodendroglia under physiologic and pathological circumstances. Indeed, malfunctioning of astrocytes represents an important factor contributing to brain injury. However, the molecular pathways of this astroglial dysfunction are poorly defined.

Repetitive Erythropoietin Treatment Improves Long-Term Neurocognitive Outcome by Attenuating Hyperoxia-Induced Hypomyelination in the Developing Brain.

Preterm infants born before 28 weeks of gestation are at high risk of neurodevelopmental impairment in later life. Cerebral white and gray matter injury is associated with adverse outcomes. High oxygen levels, often unavoidable in neonatal intensive care, have been identified as one of the main contributing factors to preterm brain injury.

Prevention of Oxygen-Induced Inflammatory Lung Injury by Caffeine in Neonatal Rats.

Background: Preterm birth implies an array of respiratory diseases including apnea of prematurity and bronchopulmonary dysplasia (BPD). Caffeine has been introduced to treat apneas but also appears to reduce rates of BPD. Oxygen is essential when treating preterm infants with respiratory problems but high oxygen exposure aggravates BPD.

Vascular endothelial growth factor polymorphism rs2010963 status does not affect patent ductus arteriosus incidence or cyclooxygenase inhibitor treatment success in preterm infants.

Background: Vascular endothelial growth factor is critically involved in ductus arteriosus closure. Polymorphisms in the vascular endothelial growth factor gene have been associated with several diseases in neonates and adults.

Aim: Herein, we investigated if vascular endothelial growth factor polymorphism rs2010963 status is associated with patent ductus arteriosus incidence and/or pharmacological treatment success.

Antioxidative effects of caffeine in a hyperoxia-based rat model of bronchopulmonary dysplasia.

Background: While additional oxygen supply is often required for the survival of very premature infants in intensive care, this also brings an increasing risk of progressive lung diseases and poor long-term lung outcomes. Caffeine is administered to neonates in neonatal intensive care for the prevention and treatment of apneas and has been shown to reduce BPD incidence and the need for mechanical ventilation, although it is still unclear whether this is due to a direct pulmonary action via antagonism of adenosine receptors and/or an indirect action. This experimental study aims to investigate the action of caffeine on the oxidative stress response in pulmonary tissue in a hyperoxia-based model of bronchopulmonary dysplasia in newborn rats.

Transient Improvement of Cerebellar Oligodendroglial Development in a Neonatal Hyperoxia Model by PDGFA Treatment.

In preterm infants, the changes from fetal life to ex-utero conditions often coincide with reduced growth and white matter damage of the cerebellum. The premature increase in arterial oxygen tension caused by preterm birth may dysregulate cerebellar development. In a hyperoxia rat model of white matter damage to mimic a steep increase in oxygen levels by 24 h exposure to 80% O from postnatal day 6 (P6) to day 7, we analyzed growth factor (GF) synthesis of cerebellar astrocytes.

Physostigmine Restores Impaired Autophagy in the Rat Hippocampus after Surgery Stress and LPS Treatment.

Tissue damage and pathogen invasion during surgical trauma have been identified as contributing factors leading to neuroinflammation in the hippocampus, which can be protected by stimulation of the cholinergic anti-inflammatory pathway using the acetylcholinesterase inhibitor physostigmine. Macroautophagy, an intracellular degradation pathway used to recycle and eliminate damaged proteins and organelles by lysosomal digestion, seems to be important for cell survival under stress conditions. This study aimed to examine the role of autophagy in physostigmine-mediated hippocampal cell protection in a rat model of surgery stress.

Caffeine Protects Against Anticonvulsant-Induced Impaired Neurogenesis in the Developing Rat Brain.

In preterm infants, phenobarbital is the first-line antiepileptic drug for neonatal seizures while caffeine is used for the treatment of apnea. Data from experimental animals suggest that phenobarbital and other anticonvulsants are toxic for the developing brain, while neuroprotective effects have been reported for caffeine both in newborn rodents and preterm human infants. To characterize the interaction of phenobarbital and caffeine in the hippocampus of the developing rodent brain, we examined the effects of both drugs given separately or together on postnatal neurogenesis after administration to neonatal rats throughout postnatal day (P) 4 to P6.

Dexmedetomidine Prevents Lipopolysaccharide-Induced MicroRNA Expression in the Adult Rat Brain.

During surgery or infection, peripheral inflammation can lead to neuroinflammation, which is associated with cognitive impairment, neurodegeneration, and several neurodegenerative diseases. Dexmedetomidine, an α-2-adrenoceptor agonist, is known to exert anti-inflammatory and neuroprotective properties and reduces the incidence of postoperative cognitive impairments. However, on the whole the molecular mechanisms are poorly understood.