newborn hypoxia early marke

Most mammals have a poor tolerance to hypoxia, and prolonged O2 restriction can lead to organ injury, particularly during fetal and early postnatal life. Nevertheless, the llama (Lama Glama) has evolved efficient mechanisms to adapt to acute and chronic perinatal hypoxia. One striking adaptation is the marked peripheral vasoconstriction measured in the llama fetus in response to acute hypoxia, which allows efficient redistribution of cardiac output towards the fetal heart and adrenal glands. This strong peripheral vasoconstrictor tone is triggered by a carotid body reflex and critically depends on α-adrenergic signaling...

Neonatal lambs, as other neonates, have physiologically a very low plasma melatonin concentration throughout 24 h. Previously, we found that melatonin given to neonates daily for 5 days decreased heart weight and changed plasma cortisol and gene expression in the adrenal and heart. Whether these changes could compromise the responses to life challenges is unknown. Therefore, firstly, we studied acute effects of melatonin on the defense mechanisms to acute hypoxia in the neonate. Eleven lambs, 2 weeks old, were instrumented and subjected to an episode of acute isocapnic hypoxia, consisting of four 30 min periods: normoxia (room air), normoxia after an i...

Neonatal cerebral hypoxia-ischemia (HI) is a major cause of neurological disorders and the most common cause of death and permanent disability worldwide, affecting 1-2/1000 live term births and up to 60% of preterm births. The Levine-Rice is the main experimental HI model; however, critical variables such as the age of animals, sex and hemisphere damaged still receive little attention in experimental design. We here investigated the influence of sex and hemisphere injured on the functional outcomes and tissue damage following early (hypoxia-ischemia performed at postnatal day 3 (HIP3)) and late (hypoxia-ischemia performed at postnatalday 7 (HIP7)) HI injury in rats...

Endoplasmic reticulum (ER) stress is implicated in the pathophysiology of various cardiovascular diseases, but the role of ER stress in cardiac rupture and/or remodeling after myocardial infarction (MI) is still unclear. Here we investigated whether ER stress plays a major role for these processes in mice. We ligated the left coronary artery (LCA) without reperfusion in mice and administered either NaCl or 4-phenylbutyric acid (4-PBA, 20 mg/kg/d) intraperitoneally for 4 weeks. Cardiac rupture rates during the first week of MI were 37...

OBJECTIVE: The effect of the 2003 severe pediatric traumatic brain injury (TBI) guidelines on outcomes has not been examined. We aimed to develop a set of acute care guideline-influenced clinical indicators of adherence and tested the relationship between these indicators during the first 72 hours after hospital admission and discharge outcomes. DESIGN: Retrospective multicenter cohort study. SETTING: Five regional pediatric trauma centers affiliated with academic medical centers...

Moderate to severe neonatal hypoxic ischemic encephalopathy remains an important cause of infant death and childhood disability. Early and accurate diagnosis of encephalopathy is difficult but critical for timely intervention. Thus, we have utilized a clinically relevant large animal model of asphyxia in-utero, followed by immediate lamb delivery, resuscitation and clinical care over the next 72h for assessment of potential biomarkers of brain injury. In-utero asphyxia was induced in twelve near-term lambs and outcomes compared with seven controls...

Activin A, a member of the transforming growth factor-β superfamily, is stimulated early in inflammation via the Toll-like receptor (TLR) 4 signalling pathway, which is also activated in myocardial ischaemia-reperfusion. Neutralising activin A by treatment with the activin-binding protein, follistatin, reduces inflammation and mortality in several disease models. This study assesses the regulation of activin A and follistatin in a murine myocardial ischaemia-reperfusion model and determines whether exogenous follistatin treatment is protective against injury...

OBJECTIVE: The evaluation of the expression of S100B protein, in the swine heart in an experimental model of hypoxia - reoxygenation. METHODS: Normocapnic hypoxia was induced in 40 male Landrace/Large White neonatal piglets by decreasing the inspired concentration of oxygen to 6-8%. When animals developed bradycardia or severe hypotension, reoxygenation was initiated. Piglets were allocated in four groups of 10, according to the oxygen concentration they were reoxygenated with: Group 1, 2, 3 and 4 resuscitated with 18%, 21%, 40% and 100% oxygen, respectively...

BACKGROUND: The neurovascular unit encompasses the functional interactions of cerebrovascular and brain parenchymal cells necessary for the metabolic homeostasis of neurons. Previous studies indicated marked but only transient (1-4 h) reactive oxygen species-dependent neurovascular dysfunction in newborn pigs after severe hypoxic/ischemic (H/I) stress contributing to the neuronal injury after birth asphyxia. OBJECTIVES: Our major purpose was to determine if neurovascular dysfunction would also occur later, at 24 h after a milder H/I stress...

Whereas brief acute or intermittent episodes of hypoxia have been shown to exert a protective role in the central nervous system and to stimulate neurogenesis, other studies suggest that early hypoxia may constitute a risk factor that influences the future development of mental disorders. We therefore investigated the effects of a neonatal "conditioning-like" hypoxia (100% N₂, 5 min) on the brain and the cognitive outcomes of rats until 720 days of age (physiologic senescence). We confirmed that such a short hypoxia led to brain neurogenesis within the ensuing weeks, along with reduced apoptosis in the hippocampus involving activation of Erk1/2 and repression of p38 and death-associated protein (DAP) kinase...

BACKGROUND: We have previously shown an increased incidence of intermittent hypoxemia (IH) events in preterm infants with severe retinopathy of prematurity (ROP). Animal models suggest that patterns of IH events may play a role in ROP severity as well. We hypothesize that specific IH event patterns are associated with ROP in preterm infants. METHODS: Variability in IH event duration, severity, and the time interval between IH events (≤80%, ≥10 s, and ≤3 min) along with the frequency spectrum of the oxygen saturation (SpO2) waveform were assessed...

Birth asphyxia results in a significant percentage of neonatal morbidity and mortality. A key factor in the management of this complication is the early and accurate detection of brain damage following asphyxia. Currently, reliable tools for such diagnosis are absent. Extensive research has focused on biomarkers in an attempt to solve this matter. Recent data marked serum and urine elevation of the S100B protein as an established peripheral biomarker for detection of brain injury including traumatic head injuries and brain damage following cardiac arrest and stroke...

Hypoxia-inducible factor 1α (HIF-1α) is a transcription factor that plays a key role in regulating the adaptive response to hypoxia. HIF-1α is stabilised during hypoxia and, after dimerisation with hypoxia-inducible factor 1β (HIF-1β), triggers the expression of various genes involved in cell cycle control and energy metabolism associated with cell survival. However, HIF-1α also regulates the expression of proapoptotic genes. The aim of this study was to ascertain the influence of HIF-1α on neurotoxicity evoked by hypoxia in rat cortical neurons...

Hypoxic-ischemic (H-I) injury to the developing brain is a significant cause of morbidity and mortality in humans. Other than hypothermia, there is no effective treatment to prevent or lessen the consequences of neonatal H-I. Increased expression of the NAD synthesizing enzyme nicotinamide mononucleotide adenylyl transferase 1 (Nmnat1) has been shown to be neuroprotective against axonal injury in the peripheral nervous system. To investigate the neuroprotective role of Nmnat1 against acute neurodegeneration in the developing CNS, we exposed wild-type mice and mice overexpressing Nmnat1 in the cytoplasm (cytNmnat1-Tg mice) to a well-characterized model of neonatal H-I brain injury...

Understanding how arterial remodeling changes the mechanical behavior of pulmonary arteries (PAs) is important to the evaluation of pulmonary vascular function. Early and current efforts have focused on the arteries' histological changes, their mechanical properties under in vitro mechanical testing, and their zero-stress and no-load states. However, the linkage between the histology and mechanical behavior is still not well understood. To explore this linkage, we investigated the geometry, residual stretch, and histology of proximal PAs in both adult rat and neonatal calf hypoxic models of pulmonary hypertension (PH), compared their changes due to chronic hypoxia across species, and proposed a two-layer mechanical model of artery to relate the opening angle to the stiffness ratio of the PA outer to inner layer...

INTRODUCTION: Alterations of dopamine in striatal presynaptic terminals play an important role in the hypoxic-ischemic (HI) brain injury. Quantification of DAT levels in the presynaptic site using (11)C-N-2-carbomethoxy-3-(4-fluorophenyl)-tropane ((11)C-CFT) with positron emission tomography (PET) was applied in studies for Parkinson's disease. The current study investigated the changes in striatal DAT following HI brain injury in newborn piglets using (11)C-CFT PET. METHODS: Newborn piglets were subjected to occlusion of bilateral common carotid arteries for 30 min and simultaneous peripheral hypoxia...

Early reperfusion after myocardial ischemia that is essential for tissue salvage also causes myocardial and vascular injury. Cardioprotection during reperfusion therapy is an essential aspect of treating myocardial infarction. Angiopoietin-1 is an endothelial-specific angiogenic factor. The potential effects of angiopoietin-1 on cardiomyocytes and vascular cells undergoing reperfusion have not been investigated. We propose a protective mechanism whereby angiopoietin-1 increases the integrity of the endothelial lining and exerts a direct survival effect on cardiomyocytes under myocardial ischemia followed by reperfusion...

Damage to major white matter tracts is a hallmark mark feature of hypoxic-ischemic (HI) brain injury in the preterm neonate. There is, however, no therapeutic intervention to treat this injury. Neuroinflammation is thought to play a prominent role in the pathogenesis of the HI-induced white matter damage but identification of the key mediators that constitute the inflammatory response remain to be fully elucidated. Cyclooxygenase enzymes (COX-1 and COX-2) are candidate neuroinflammatory mediators that may contribute to the HI-induced demise of early oligodendrocyte progenitors and myelination...

BACKGROUND AND OBJECTIVE: Perioperative myocardial ischaemia leads to an exceedingly high mortality. Previous studies have indicated that propofol pre-conditioning could mimic the cardioprotective effects of ischaemic pre-conditioning. The purpose of this study was to determine whether propofol post-conditioning is cardioprotective and to explore the possible molecular mechanism of propofol post-conditioning. METHODS: Primary cultured neonatal rat cardiomyocytes were exposed to 12 h of hypoxia followed by 4 h of reoxygenation (H/R) and post-conditioned by different concentrations of propofol at the onset of reperfusion with and without a specific inhibitor of extracellular signal-regulated kinases (ERKs)...

BACKGROUND: In spite of advances in many noninvasive instruments for studying cardiac anomalies in children, cardiac catheterization (CC) is still an essential method for the precise calculation of cardiovascular hemodynamic status and for performing therapeutic interventions. Accordingly, all adverse events (AE) related to CC are a major concern to pediatric cardiologists. PATIENTS AND METHODS: A total of 220 children with congenital heart disease (CHD) who received cardiac catheterization in our tertiary care hospital between the period of January 2000 and December 2002 were studied...