New Wavelet Neurovascular Bundle for Bedside Evaluation of Cerebral Autoregulation and Neurovascular Coupling in Newborns with Hypoxic-Ischemic Encephalopathy
Neonatal encephalopathy (NE) resulting from birth asphyxia constitutes a major global public health burden for millions of infants every year, and despite therapeutic hypothermia, half of these neonates have poor neurological outcomes. As new neuroprotective interventions are being studied in clinical trials, there is a critical need to establish physiological surrogate markers of therapeutic efficacy, to guide patient selection and/or to modify the therapeutic intervention. The challenge in the field of neonatal brain injury has been the difficulty of clinically discerning NE severity within the short therapeutic window a...
Source: Developmental Neuroscience - March 29, 2017 Category: Neuroscience Source Type: research

Optimizing the Dose of Erythropoietin Required to Prevent Acute Ventilation-Induced Cerebral White Matter Injury in Preterm Lambs
Erythropoietin (EPO) is being trialed in preterm neonates for neuroprotection. We have recently demonstrated that a single high bolus dose (5,000 IU/kg) of recombinant human EPO amplified preterm lung and brain ventilation-induced injury. We aimed to determine the optimal dose of EPO to reduce ventilation-induced cerebral white matter inflammation and injury in preterm lambs. Lambs (0.85 gestation) were ventilated with an injurious strategy for 15 min followed by conventional ventilation for 105 min. Lambs were randomized to no treatment (VENT;n = 8) or received a bolus dose of EPO (EPREX ®): 300 IU/kg (EPO 300;n = 5), 1,...
Source: Developmental Neuroscience - March 27, 2017 Category: Neuroscience Source Type: research

Focal Brain Injury Associated with a Model of Severe Hypoxic-Ischemic Encephalopathy in Nonhuman Primates
We describe a cohort of 4 near-term fetalMacaca nemestrina that underwent 18 min of in utero UCO, followed by cesarean section delivery, resuscitation, and subsequent postnatal mechanical ventilation, with exposure to intermittent daily hypoxia (3 min, 8% O2 3-8 times daily for 3 days). After delivery, all animals demonstrated severe metabolic acidosis (pH 7 ± 0.12; mean ± SD) and low APGAR scores ( (Source: Developmental Neuroscience)
Source: Developmental Neuroscience - March 24, 2017 Category: Neuroscience Source Type: research

Sildenafil Enhances Quantity of Immature Neurons and Promotes Functional Recovery in the Developing Ischemic Mouse Brain
Conclusions: Here, we report that treatment with sildenafil after HI insult did not improve histological brain injury scores. Nevertheless, our results suggest involvement of the cGMP and PI3K/Akt/GSK-3 β signaling pathway with promotion of a neurogenic response and reduction of neurological deficits. In summary, sildenafil may have a role in promoting recovery from HI injury in the developing brain.Dev Neurosci (Source: Developmental Neuroscience)
Source: Developmental Neuroscience - March 24, 2017 Category: Neuroscience Source Type: research

Susceptibility-Weighted Imaging Identifies Iron-Oxide-Labeled Human Neural Stem Cells: Automated Computational Detection
Neonatal hypoxic-ischemic brain injury (HII) can lead to devastating neurological outcomes such as cerebral palsy, epilepsy, and mental retardation. Human neural stem cell (hNSC) therapy provides new hope for the treatment of neonatal HII. These multipotent cells can aid in HII recovery by activating multiple reparative mechanisms including secretion of neurotrophic factors that enhance brain repair and plasticity. For clinical use of implanted hNSCs, methods are required to identify, quantify, track, and visualize migration and replication in an automated and reproducible fashion. In the current study, we used a model of ...
Source: Developmental Neuroscience - March 24, 2017 Category: Neuroscience Source Type: research

Moderate-Grade Germinal Matrix Haemorrhage Activates Cell Division in the Neonatal Mouse Subventricular Zone
Precise temporal and spatial control of the neural stem/progenitor cells within the subventricular zone (SVZ) germinal matrix of the brain is important for normal development in the third trimester and the early postnatal period. The high metabolic demands of proliferating germinal matrix precursors, coupled with the flimsy structure of the germinal matrix cerebral vasculature, are thought to account for the high rates of haemorrhage in extremely- and very-low-birth-weight preterm infants. Germinal matrix haemorrhage can commonly extend to intraventricular haemorrhage (IVH). Because neural stem/progenitor cells are sensiti...
Source: Developmental Neuroscience - March 24, 2017 Category: Neuroscience Source Type: research

Proteomic Analysis of Mouse Cortex Postsynaptic Density following Neonatal Brain Hypoxia-Ischemia
Proteomics of the synapses and postsynaptic densities (PSDs) have provided a deep understanding of protein composition and signal networks in the adult brain, which underlie neuronal plasticity and neurodegenerative or psychiatric disorders. However, there is a paucity of knowledge about the architecture and organization of PSDs in the immature brain, and how it is modified by brain injury in an early developing stage. Mass spectrometry (MS)-based proteomic analysis was performed on PSDs prepared from cortices of postnatal day 9 na ïve mice or pups which had suffered hypoxic-ischemic (HI) brain injury. 512 proteins of dif...
Source: Developmental Neuroscience - March 17, 2017 Category: Neuroscience Source Type: research

Cerebrospinal Fluid and Parenchymal Brain Development and Growth in the Healthy Fetus
The objective of this study was to apply quantitative magnetic resonance imaging to characterize absolute cerebrospinal fluid (CSF) development, as well as its relative development to fetal brain parenchyma in the healthy human fetus.Design: We created three-dimensional high-resolution reconstructions of the developing brain for healthy fetuses between 18 and 40 weeks' gestation, segmented the parenchymal and CSF spaces, and calculated the volumes for the lateral, third, and fourth ventricles; extra-axial CSF space; and the cerebrum, cerebellum, and brainstem. From these data, we constructed normograms of the resulting vol...
Source: Developmental Neuroscience - March 17, 2017 Category: Neuroscience Source Type: research

Early- versus Late-Onset Fetal Growth Restriction Differentially Affects the Development of the Fetal Sheep Brain
Fetal growth restriction (FGR) is a common complication of pregnancy, principally caused by suboptimal placental function, and is associated with high rates of perinatal mortality and morbidity. Clinical studies suggest that the time of onset of placental insufficiency is an important contributor towards the neurodevelopmental impairments that are evident in children who had FGR. It is however currently unknown how early-onset and late-onset FGR differentially affect brain development. The aim of this study was to examine neuropathology in early-onset and late-onset FGR fetal sheep and to determine whether they differentia...
Source: Developmental Neuroscience - March 8, 2017 Category: Neuroscience Source Type: research

Dedifferentiated Fat Cells as a Novel Source for Cell Therapy to Target Neonatal Hypoxic-Ischemic Encephalopathy
Neonatal hypoxic-ischemic (HI) encephalopathy (HIE) remains a major cause of mortality and persistent neurological disabilities in affected individuals. At present, hypothermia is considered to be the only applicable treatment option, although growing evidence suggests that cell-based therapy might achieve better outcomes. Dedifferentiated fat (DFAT) cells are derived from mature adipocytes via a dedifferentiation strategy called ceiling culture. Their abundance and ready availability might make them an ideal therapeutic tool for the treatment of HIE. In the present study, we aimed to determine whether the outcome of HIE c...
Source: Developmental Neuroscience - March 8, 2017 Category: Neuroscience Source Type: research

Neuroprotective Effects of Acetyl- < smlcap > L < /smlcap > -Carnitine on Neonatal Hypoxia Ischemia-Induced Brain Injury in Rats
Perinatal hypoxia ischemia (HI) is a significant cause of brain injury in surviving infants. Although hypothermia improves outcomes in some infants, additional therapies are needed since about 40% of infants still have a poor outcome. Acetyl-L-carnitine (ALCAR), an acetylated derivative ofL-carnitine, protected against early changes in brain metabolites and mitochondrial function after HI on postnatal day (PND) 7 in a rat pup model of near-term HI injury. However, its efficacy in long-term structural and functional outcomes remains unexplored. We determined the efficacy of ALCAR therapy administered to rat pups after HI at...
Source: Developmental Neuroscience - February 22, 2017 Category: Neuroscience Source Type: research

Restraint Stress during Pregnancy Rapidly Raises Kynurenic Acid Levels in Mouse Placenta and Fetal Brain
Stressful events during pregnancy adversely affect brain development and may increase the risk of psychiatric disorders later in life. Early changes in the kynurenine (KYN) pathway (KP) of tryptophan (TRP) degradation, which contains several neuroactive metabolites, including kynurenic acid (KYNA), 3-hydroxykynurenine (3-HK), and quinolinic acid (QUIN), may constitute a molecular link between prenatal stress and delayed pathological consequences. To begin testing this hypothesis experimentally, we examined the effects of a 2-h restraint stress on KP metabolism in pregnant FVB/N mice on gestational day 17. TRP, KYN, KYNA, 3...
Source: Developmental Neuroscience - February 17, 2017 Category: Neuroscience Source Type: research

Early Development of Parvalbumin-, Somatostatin-, and Cholecystokinin-Expressing Neurons in Rat Brain following Prenatal Immune Activation and Maternal Iron Deficiency
This study used a rat model to test whether prenatal immune activation with lipopolysaccharide (LPS; at gestation days, GD, 15 and 16) or maternal iron deficiency (from GD2 to postnatal day P7) or the combination of both insults alters major subtypes of GABAergic interneurons (parvalbumin, somatostatin, cholecystokinin) in brain regions relevant to schizophrenia (medial and dorsolateral prefrontal cortex [PFC], hippocampal CA1 and dentate gyrus, ventral subiculum) in offspring at P14 or P28. Prenatal LPS treatment significantly increased the density of parvalbumin-immunoreactive neurons at P14 in the medial PFC, dorsolater...
Source: Developmental Neuroscience - February 17, 2017 Category: Neuroscience Source Type: research

Therapeutic Hypothermia Provides Variable Protection against Behavioral Deficits after Neonatal Hypoxia-Ischemia: A Potential Role for Brain-Derived Neurotrophic Factor
Conclusions: TH provides benefit in specific domains of behavior following neonatal HI. In general, these benefits accrued to both males and females, but not in all areas. In some domains, such as memory, no benefit of TH was found. Late differences in individual BDNF levels may explain some of these findings.Dev Neurosci (Source: Developmental Neuroscience)
Source: Developmental Neuroscience - February 14, 2017 Category: Neuroscience Source Type: research

Hyperoxia and the Immature Brain
Despite major advances in obstetrics and neonatal intensive care, preterm infants frequently suffer from neurological impairments in later life. Preterm and also full-term neonates are generally susceptible to injury caused by reactive oxygen species due to the immaturity of endogenous radical scavenging systems. It is well known that high oxygen levels experienced during the critical phase of maturation can profoundly influence developmental processes. Supraphysiological oxygen concentrations used for resuscitation or in the care of critically ill infants are known to have deleterious effects on the developing lung and re...
Source: Developmental Neuroscience - February 2, 2017 Category: Neuroscience Source Type: research