Synergistic Action of Presynaptic Muscarinic Acetylcholine Receptors and Adenosine Receptors in Developmental Axonal Competition at the Neuromuscular Junction
The development of the nervous system involves the initial overproduction of synapses, which promotes connectivity. Hebbian competition between axons with different activities leads to the loss of roughly half of the overproduced elements and this refines connectivity. We used quantitative immunohistochemistry to investigate, in the postnatal day 7 (P7) to P9 neuromuscular junctions, the involvement of muscarinic receptors (muscarinic acetylcholine autoreceptors and the M1, M2, and M4 subtypes) and adenosine receptors (A1 and A2A subtypes) in the control of axonal elimination after the mouse levator auris longus muscle had...
Source: Developmental Neuroscience - April 26, 2017 Category: Neuroscience Source Type: research

Erythropoietin Treatment Exacerbates Moderate Injury after Hypoxia-Ischemia in Neonatal Superoxide Dismutase Transgenic Mice
This study confirms our previous results showing greater injury with SOD overexpression in the neonatal brain after HI at P7 in a different strain. These results also suggest that EPO treatment cannot ameliorate the damage seen in situations where there is excess H2O2 accumulation, and it may exacerbate injury in settings of extreme oxidative stress.Dev Neurosci (Source: Developmental Neuroscience)
Source: Developmental Neuroscience - April 26, 2017 Category: Neuroscience Source Type: research

Hypoxic-Ischaemic Encephalopathy and the Blood-Brain Barrier in Neonates
This review aims to highlight a possible relationship between hypoxic-ischaemic encephalopathy (HIE) and the disruption of the blood-brain barrier (BBB). Inflammatory reactions perpetuate a large proportion of cerebral injury. The extent of injury noted in HIE is not only determined by the biochemical cascades that trigger the apoptosis-necrosis continuum of cell death in the brain parenchyma, but also by the breaching of the BBB by pro-inflammatory factors. We examine the changes that contribute to the breakdown of the BBB that occur during HIE at a macroscopic, cellular, and molecular level. The BBB is a permeability bar...
Source: Developmental Neuroscience - April 21, 2017 Category: Neuroscience Source Type: research

Unbiased Quantification of Subplate Neuron Loss following Neonatal Hypoxia-Ischemia in a Rat Model
Conclusions: There is significant biological variability inherent in both the subplate neuron cell number and the pattern and severity of cortical injury following HI at P2 in rats. Despite this variability, the subplate neuron cell number is lower following P2 HI in animals with mild or moderate cortical injury, whereas the middle-to-lower-layer cortical neuronal number is unchanged. In more severe cases, neurons are lost from the lower cortical layers, suggesting a relative vulnerability of subplate neurons.Dev Neurosci (Source: Developmental Neuroscience)
Source: Developmental Neuroscience - April 21, 2017 Category: Neuroscience Source Type: research

Dietary Selenium or Zinc Supplementation Restores Brain Lipid Composition and Membrane Fluidity in Protein-Undernourished Rats
Studies have shown that protein undernutrition (PU) modifies the membrane lipid composition in the intestine and liver, as well as in plasma and other areas. However, there is limited information on the effect of PU on synaptosomal membrane lipid composition and fluidity and the protective role of selenium (Se) and zinc (Zn), which is a major focus of the present study. For 10 weeks, rats were fed diets containing 16% casein, which constituted the adequate protein diet, or 5% casein, representing the PU diet. The animals were supplemented with Se and Zn at a concentration of 0.15 and 227 mg L-1, respectively, in drinking w...
Source: Developmental Neuroscience - April 20, 2017 Category: Neuroscience Source Type: research

Hypothermic Neuronal Rescue from Infection-Sensitised Hypoxic-Ischaemic Brain Injury Is Pathogen Dependent
Perinatal infection increases the vulnerability of the neonatal brain to hypoxic-ischaemic (HI) injury. Hypothermia treatment (HT) does not provide neuroprotection after pre-insult inflammatory sensitisation by lipopolysaccharide (LPS), a gram-negative bacterial wall constituent. However, early-onset sepsis in term babies is caused by gram-positive species in more than 90% of cases, and neuro-inflammatory responses triggered through the gram-negative route (Toll-like receptor 4, TLR-4) are different from those induced through the gram-positive route via TLR-2. Whether gram-positive septicaemia sensitises the neonatal brain...
Source: Developmental Neuroscience - April 13, 2017 Category: Neuroscience Source Type: research

Implicating Receptor Activator of NF- & #x03BA;B (RANK)/RANK Ligand Signalling in Microglial Responses to Toll-Like Receptor Stimuli
Inflammation in the perinatal brain caused by maternal or intrauterine fetal infection is now well established as an important contributor to the development of perinatal brain injury. Exposure to inflammatory products can impair perinatal brain development and act as a risk factor for neurological dysfunction, cognitive disorders, cerebral palsy, or preterm birth. Pre-exposure to inflammation significantly exacerbates brain injury caused by hypoxic/ischaemic insult. Tumour necrosis factor (TNF) is a family of cytokines largely involved in inflammation signalling. In our previous study, we identified the importance of TNF-...
Source: Developmental Neuroscience - April 12, 2017 Category: Neuroscience Source Type: research

EEG - A Valuable Biomarker of Brain Injury in Preterm Infants
This review focuses on the role of electroencephalography (EEG) in monitoring abnormalities of preterm brain function. EEG features of the most common developmental brain injuries in preterm infants, including intraventricular haemorrhage, periventricular leukomalacia, and perinatal asphyxia, are described. We outline the most common EEG biomarkers associated with these injuries, namely seizures, positive rolandic sharp waves, EEG suppression/increased interburst intervals, mechanical delta brush activity, and other deformed EEG waveforms, asymmetries, and asynchronies. The increasing survival rate of preterm infants, in p...
Source: Developmental Neuroscience - April 12, 2017 Category: Neuroscience Source Type: research

Dexmedetomidine Combined with Therapeutic Hypothermia Is Associated with Cardiovascular Instability and Neurotoxicity in a Piglet Model of Perinatal Asphyxia
The selective α2-adrenoreceptor agonist dexmedetomidine has shown neuroprotective, analgesic, anti-inflammatory, and sympatholytic properties that may be beneficial in neonatal encephalopathy (NE). As therapeutic hypothermia is only partially effective, adjunct therapies are needed to optimize outcomes. The aim was to assess whether hypothermia + dexmedetomidine treatment augments neuroprotection compared to routine treatment (hypothermia + fentanyl sedation) in a piglet model of NE using magnetic resonance spectroscopy (MRS) biomarkers, which predict outcomes in babies with NE, and immunohistochemistry. After hypoxia-isc...
Source: Developmental Neuroscience - April 11, 2017 Category: Neuroscience Source Type: research

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