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Developmental Neuroscience

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https://www.readbyqxmd.com/read/28511187/the-differential-effects-of-erythropoietin-exposure-to-oxidative-stress-on-microglia-and-astrocytes-in-vitro
#1
Praneeti Pathipati, Donna M Ferriero
The neonatal brain is especially susceptible to oxidative stress owing to its reduced antioxidant capacity. Following hypoxic-ischemic (HI) injury, for example, there is a prolonged elevation in levels of hydrogen peroxide (H2O2) in the immature brain compared to the adult brain, resulting in lasting injury that can lead to life-long disability or morbidity. Erythropoietin (Epo) is one of few multifaceted treatment options that have been promising enough to trial in the clinic for both term and preterm brain injury...
May 17, 2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/28494460/persistently-altered-metabolic-phenotype-following-perinatal-excitotoxic-brain-injury
#2
Benjamin J Blaise, Leslie Schwendimann, Vibol Chhor, Vincent Degos, Mark P Hodson, Guido Dallmann, Matthias Keller, Pierre Gressens, Bobbi Fleiss
Excitotoxicity plays a key role during insults to the developing brain such as neonatal encephalopathy, stroke, and encephalopathy of prematurity. Such insults affect many thousands of infants each year. Excitotoxicity causes frank lesions due to cell death and gliosis and disturbs normal developmental process, leading to deficits in learning, memory, and social integration that persist into adulthood. Understanding the underlying processes of the acute effects of excitotoxicity and its persistence during brain maturation provides an opportunity to identify mechanistic or diagnostic biomarkers, thus enabling and designing possible therapies...
May 12, 2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/28490023/cord-blood-il-16-is-associated-with-3-year-neurodevelopmental-outcomes-in-perinatal-asphyxia-and-hypoxic-ischaemic-encephalopathy
#3
Caroline E Ahearne, Ruby Y Chang, Brian H Walsh, Geraldine B Boylan, Deirdre M Murray
Activation of the inflammatory pathway is increasingly recognized as an important mechanism of injury following neonatal asphyxia and encephalopathy. This process may contribute to the poor prognosis seen in some cases, despite therapeutic hypothermia. Our group has previously identified raised interleukin (IL)-6 and IL-16, measured in umbilical cord blood at birth, to be predictive of grade of hypoxic-ischaemic encephalopathy (HIE). Our aim in this study was to examine the ability of these cytokines to predict the 3-year neurodevelopmental outcome in the same cohort...
May 11, 2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/28490020/maternal-inflammation-results-in-altered-tryptophan-metabolism-in-rabbit-placenta-and-fetal-brain
#4
Monica Williams, Zhi Zhang, Elizabeth Nance, Julia L Drewes, Wojciech G Lesniak, Sarabdeep Singh, Diane C Chugani, Kannan Rangaramanujam, David R Graham, Sujatha Kannan
Maternal inflammation has been linked to neurodevelopmental and neuropsychiatric disorders such as cerebral palsy, schizophrenia, and autism. We had previously shown that intrauterine inflammation resulted in a decrease in serotonin, one of the tryptophan metabolites, and a decrease in serotonin fibers in the sensory cortex of newborns in a rabbit model of cerebral palsy. In this study, we hypothesized that maternal inflammation results in alterations in tryptophan pathway enzymes and metabolites in the placenta and fetal brain...
May 11, 2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/28490013/sulfatase-2-modulates-fate-change-from-motor-neurons-to-oligodendrocyte-precursor-cells-through-coordinated-regulation-of-shh-signaling-with-sulfatase-1
#5
Wen Jiang, Yugo Ishino, Hirokazu Hashimoto, Kazuko Keino-Masu, Masayuki Masu, Kenji Uchimura, Kenji Kadomatsu, Takeshi Yoshimura, Kazuhiro Ikenaka
Sulfatases (Sulfs) are a group of endosulfatases consisting of Sulf1 and Sulf2, which specifically remove sulfate from heparan sulfate proteoglycans. Although several studies have shown that Sulf1 acts as a regulator of sonic hedgehog (Shh) signaling during embryonic ventral spinal cord development, the detailed expression pattern and function of Sulf2 in the spinal cord remains to be determined. In this study, we found that Sulf2 also modulates the cell fate change from motor neurons (MNs) to oligodendrocyte precursor cells (OPCs) by regulating Shh signaling in the mouse ventral spinal cord in coordination with Sulf1...
May 11, 2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/28486224/long-term-neuropathological-changes-associated-with-cerebral-palsy-in-a-nonhuman-primate-model-of-hypoxic-ischemic-encephalopathy
#6
Ryan M McAdams, Bobbi Fleiss, Christopher Traudt, Leslie Schwendimann, Jessica M Snyder, Robin L Haynes, Niranjana Natarajan, Pierre Gressens, Sandra E Juul
BACKGROUND: Cerebral palsy (CP) is the most common motor disability in childhood, with a worldwide prevalence of 1.5-4/1,000 live births. Hypoxic-ischemic encephalopathy (HIE) contributes to the burden of CP, but the long-term neuropathological findings of this association remain limited. METHODOLOGY: Thirty-four term Macaca nemestrina macaques were included in this long-term neuropathological study: 9 control animals delivered by cesarean section and 25 animals with perinatal asphyxia delivered by cesarean section after 15-18 min of umbilical cord occlusion (UCO)...
May 10, 2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/28472809/developmental-changes-in-expression-of-gabaa-receptor-subunits-%C3%AE-1-%C3%AE-2-and-%C3%AE-3-in-the-pig-brain
#7
Stephanie M Miller, Viskasari P Kalanjati, Paul B Colditz, Stella Tracey Björkman
GABA is a major neurotransmitter in the mammalian brain. In the mature brain GABA exerts inhibitory actions via the GABAA receptor (GABAAR); however, in the immature brain GABA provides much of the excitatory drive. We examined the expression of 3 predominant GABAA α-subunit proteins in the pig brain at various pre- and postnatal ages. Brain tissue was collected from piglets born via caesarean section at preterm ages 91, 97, 100, and 104 days' gestational age (GA), at term equivalent (114 days' GA, caesarean section) and at term, postnatal day 0 (P0) (spontaneous delivery, term = 115 days)...
May 5, 2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/28467985/effects-of-antenatal-melatonin-treatment-on-the-cerebral-vasculature-in-an-ovine-model-of-fetal-growth-restriction
#8
Margie Castillo-Melendez, Tamara Yawno, Amy Sutherland, Graham Jenkin, Euan M Wallace, Suzanne L Miller
Chronic moderate hypoxia, such as occurs in fetal growth restriction (FGR) during gestation, compromises the blood-brain barrier (BBB) and results in structural abnormalities of the cerebral vasculature. We have previously determined the neuroprotective and antioxidant effects of maternal administration of melatonin (MLT) on growth-restricted newborn lambs. The potential of maternal MLT therapy for the treatment of cerebrovascular dysfunction-associated developmental hypoxia has also been demonstrated in newborn lambs...
May 4, 2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/28448983/intrauterine-growth-restriction-alters-the-postnatal-development-of-the-rat-cerebellum
#9
Annie R A McDougall, Vanny Wiradjaja, Aminath Azhan, Anqi Li, Nadia Hale, Mary E Wlodek, Stuart B Hooper, Megan J Wallace, Mary Tolcos
Intrauterine growth restriction (IUGR) is a major cause of antenatal brain injury. We aimed to characterize cerebellar deficits following IUGR and to investigate the potential underlying cellular and molecular mechanisms. At embryonic day 18, pregnant rats underwent either sham surgery (controls; n = 23) or bilateral uterine vessel ligation to restrict blood flow to fetuses (IUGR; n = 20). Offspring were collected at postnatal day 2 (P2), P7, and P35. Body weights were reduced at P2, P7, and P35 in IUGR offspring (p < 0...
April 28, 2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/28448965/neuroprotective-treatments-after-perinatal-hypoxic-ischemic-brain-injury-evaluated-with-magnetic-resonance-spectroscopy
#10
Hester Rijkje Berger, Eva Brekke, Marius Widerøe, Tora Sund Morken
Perinatal hypoxic-ischemic brain injury is a major health problem. Adjuvant treatments that improve the neuroprotective effect of the current treatment, therapeutic hypothermia, are urgently needed. The growing knowledge about the complex pathophysiology of hypoxia-ischemia (HI) has led to the discovery of several important targets for neuroprotection. Early interventions should focus on the preservation of energy metabolism, the reduction of glutamate excitotoxicity and oxidative stress, the maintenance of calcium homeostasis, and the prevention of apoptosis...
April 28, 2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/28445884/synergistic-action-of-presynaptic-muscarinic-acetylcholine-receptors-and-adenosine-receptors-in-developmental-axonal-competition-at-the-neuromuscular-junction
#11
Laura Nadal, Neus Garcia, Erica Hurtado, Anna Simó, Marta Tomàs, Maria Angel Lanuza, Victor Cilleros, Josep Maria Tomàs
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 been exposed to selective antagonists in vivo...
April 27, 2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/28445874/erythropoietin-treatment-exacerbates-moderate-injury-after-hypoxia-ischemia-in-neonatal-superoxide-dismutase-transgenic-mice
#12
R Ann Sheldon, Christine Windsor, Byong Sop Lee, Olatz Arteaga Cabeza, Donna M Ferriero
The neonatal brain is highly susceptible to oxidative stress as developing endogenous antioxidant mechanisms are overwhelmed. In the neonate, superoxide dismutase (SOD) overexpression worsens hypoxic-ischemic injury due to H2O2 accumulation in the brain. Erythropoietin (EPO) is upregulated in 2 phases after HI, early (4 h) and late (7 days), and exogenous EPO has been effective in reducing the injury, possibly through reducing oxidative stress. We hypothesized that exogenous EPO would limit injury from excess H2O2 seen in SOD1-overexpressing mice, and thus enhance recovery after HI...
April 27, 2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/28434009/hypoxic-ischaemic-encephalopathy-and-the-blood-brain-barrier-in-neonates
#13
Wei Ling Amelia Lee, Adina T Michael-Titus, Divyen K Shah
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...
April 22, 2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/28434006/unbiased-quantification-of-subplate-neuron-loss-following-neonatal-hypoxia-ischemia-in-a-rat-model
#14
Alexandra Mikhailova, Naveena Sunkara, Patrick S McQuillen
BACKGROUND: Cellular targets of neonatal hypoxia-ischemia (HI) include both oligodendrocyte and neuronal lineages with differences in the patterns of vulnerable cells depending upon the developmental stage at which the injury occurs. Injury to the developing white matter is a characteristic feature of human preterm brain injury. Data are accumulating, however, for neuronal injury in the developing cerebral cortex. In the most widely used rodent model of preterm HI brain injury, conflicting data have been reported regarding the sensitivity of subplate neurons to early neonatal HI, with some reports of selective vulnerability and others that find no increased loss of subplate neurons in comparison with other cortical layers...
April 22, 2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/28427058/dietary-selenium-or-zinc-supplementation-restores-brain-lipid-composition-and-membrane-fluidity-in-protein-undernourished-rats
#15
Olusegun L Adebayo, Bamidele A Salau, Rajat Sandhir, Gbenga A Adenuga
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...
April 21, 2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/28407632/hypothermic-neuronal-rescue-from-infection-sensitised-hypoxic-ischaemic-brain-injury-is-pathogen-dependent
#16
Mari Falck, Damjan Osredkar, Elke Maes, Torun Flatebø, Thomas Ragnar Wood, Hemmen Sabir, Marianne Thoresen
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...
April 14, 2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/28402972/eeg-a-valuable-biomarker-of-brain-injury-in-preterm-infants
#17
Elena Pavlidis, Rhodri O Lloyd, Geraldine B Boylan
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...
April 13, 2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/28402971/implicating-receptor-activator-of-nf-%C3%AE%C2%BAb-rank-rank-ligand-signalling-in-microglial-responses-to-toll-like-receptor-stimuli
#18
Anton Kichev, Pascale Eede, Pierre Gressens, Claire Thornton, Henrik Hagberg
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...
April 13, 2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/28391258/dexmedetomidine-combined-with-therapeutic-hypothermia-is-associated-with-cardiovascular-instability-and-neurotoxicity-in-a-piglet-model-of-perinatal-asphyxia
#19
Mojgan Ezzati, Go Kawano, Eridan Rocha-Ferreira, Daniel Alonso-Alconada, Jane K Hassell, Kevin D Broad, Igor Fierens, Bobbi Fleiss, Alan Bainbridge, David L Price, Pardis Kaynezhad, Brian Anderson, Mariya Hristova, Ilias Tachtsidis, Xavier Golay, Pierre Gressens, Robert D Sanders, Nicola J Robertson
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...
April 8, 2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/28355608/new-wavelet-neurovascular-bundle-for-bedside-evaluation-of-cerebral-autoregulation-and-neurovascular-coupling-in-newborns-with-hypoxic-ischemic-encephalopathy
#20
Lina F Chalak, Rong Zhang
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 after birth or of analyzing the dynamic aspects of the cerebral circulation in sick NE newborns...
March 30, 2017: Developmental Neuroscience
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