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fetal neuroprotection

Reshama Navathe, Vincenzo Berghella
PURPOSE OF REVIEW: Tocolytic agents have been used for over 60 years in the fight against preterm labor, which ultimately can lead to preterm birth. Currently, clinicians can choose from a variety of drug classes to achieve the primary goal of delaying delivery by 48 h, thereby allowing time for administration of corticosteroids for fetal lung maturity, and if appropriate, starting magnesium sulfate for fetal neuroprotection. However, there are currently no known therapies to maintain the tocolytic effect beyond those initial 48 h...
October 18, 2016: Current Opinion in Obstetrics & Gynecology
Priya Revathikumar, Filip Bergqvist, Srividya Gopalakrishnan, Marina Korotkova, Per-Johan Jakobsson, Jon Lampa, Erwan Le Maître
BACKGROUND: The cholinergic anti-inflammatory pathway (CAP) primarily functions through acetylcholine (ACh)-alpha7 nicotinic acetylcholine receptor (α7nAChR) interaction on macrophages to control peripheral inflammation. Interestingly, ACh can also bind α7nAChRs on microglia resulting in neuroprotective effects. However, ACh effects on astrocytes remain elusive. Here, we investigated the effects of nicotine, an ACh receptor agonist, on the cytokine and cholinesterase production of immunocompetent human astrocytes stimulated with interleukin 1β (IL-1β) in vitro...
September 29, 2016: Journal of Neuroinflammation
Rola Aldana Bekdash
Choline is an essential nutrient that is required for normal development of the brain. Via its metabolite betaine, it participates in the synthesis of S-adenosylmethionine, a major methyl donor for histone and DNA methylation, two epigenetic mechanisms that regulate gene expression and may alter brain function. Besides its role in methyl group metabolism, choline also has pivotal functions, including the maintenance of structural integrity of membranes and modulation of cholinergic neurotransmission, functions that are often dysregulated in some neurodegenerative disorders...
2016: Advances in Neurobiology
Mariya S Spasova, Xiaodi Chen, Grazyna B Sadowska, Edward R Horton, Yow-Pin Lim, Barbara S Stonestreet
Hypoxic-ischemic (HI) brain injury is a major cause of neurological abnormalities in the perinatal period. Inflammation contributes to the evolution of HI brain injury. Inter-alpha inhibitor proteins (IAIPs) are a family of proteins that are part of the innate immune system. We have reported that endogenous IAIPs exhibit developmental changes in ovine brain and that exogenous IAIP treatment reduces neuronal death in HI neonatal rats. However, the effects of HI on endogenous IAIPs in brain have not been previously examined...
September 12, 2016: Developmental Neurobiology
Audrey Binette, Simon Blouin, Amélie Ardilouze, Jean-Charles Pasquier
OBJECTIVE: Antenatal magnesium sulfate (MgSO4) is recommended for fetal neuroprotection. The aim of this animal study was to assess the neuroprotective effect of in utero exposure to MgSO4, under inflammatory conditions. METHODS: Timed pregnant Sprague-Dawley (SD) rats (n = 29) received four intra-peritoneal (IP) injections of lipopolysaccharides (LPS; 200 μg/kg), combined with increasing concentrations of MgSO4 (25, 50 or 100 mg/kg, n = 19) or saline solution (SS; n = 10)...
August 31, 2016: Journal of Maternal-fetal & Neonatal Medicine
Diana I Escalona-Vargas, Andrew S Thagard, Kaitlin McGrail, Peter G Napolitano, Everett F Magann, Curtis L Lowery, Hari Eswaran
No abstract text is available yet for this article.
October 2016: Prenatal Diagnosis
Kishwar Azad, Jiji Mathews
Preterm births (PTBs), defined as births before 37 weeks of gestation account for the majority of deaths in the newborn period. Prediction and prevention of PTB is challenging. A history of preterm labour or second trimester losses and accurate measurement of cervical length help to identify women who would benefit from progesterone and cerclage. Fibronectin estimation in the cervicovaginal secretions of a symptomatic woman with an undilated cervix can predict PTB within 10 days of testing. Antibiotics should be given to women with preterm prelabour rupture of membranes but tocolysis has a limited role in the management of preterm labour...
June 24, 2016: Best Practice & Research. Clinical Obstetrics & Gynaecology
Mariko Saito, Goutam Chakraborty, Maria Hui, Kurt Masiello, Mitsuo Saito
Ethanol induces neurodegeneration in the developing brain, which may partially explain the long-lasting adverse effects of prenatal ethanol exposure in fetal alcohol spectrum disorders (FASD). While animal models of FASD show that ethanol-induced neurodegeneration is associated with glial activation, the relationship between glial activation and neurodegeneration has not been clarified. This review focuses on the roles of activated microglia and astrocytes in neurodegeneration triggered by ethanol in rodents during the early postnatal period (equivalent to the third trimester of human pregnancy)...
August 16, 2016: Brain Sciences
Edoardo Parrella, Vanessa Porrini, Rosa Iorio, Marina Benarese, Annamaria Lanzillotta, Mariana Mota, Mariella Fusco, Paolo Tonin, PierFranco Spano, Marina Pizzi
The combination of palmitoylethanolamide (PEA), an endogenous fatty acid amide belonging to the family of the N-acylethanolamines, and the flavonoid luteolin has been found to exert neuroprotective activities in a variety of mouse models of neurological disorders, including brain ischemia. Indirect findings suggest that the two molecules can reduce the activation of mastocytes in brain ischemia, thus modulating crucial cells that trigger the inflammatory cascade. Though, no evidence exists about a direct effect of PEA and luteolin on mast cells in experimental models of brain ischemia, either used separately or in combination...
October 1, 2016: Brain Research
Bea Kowitzke, Gesa Cohrs, Ivo Leuschner, Arend Koch, Michael Synowitz, Hubertus Maximilian Mehdorn, Janka Held-Feindt, Friederike Knerlich-Lukoschus
Myelomeningoceles (mmc) are clinically challenging CNS malformations. Although improvement in their management has been achieved with respect to antenatal diagnosis, prevention, and fetal surgery, the cellular mechanisms of damage in the neural placode are poorly understood. We aimed to identify cellular and molecular factors in lesion amplifying cascades in mmc placodes. Seventeen mmc specimens obtained during reconstructive surgery that harbored sufficient neuroepithelial tissue were investigated. Normal adult and stillborn spinal cord tissue served as controls...
September 2016: Journal of Neuropathology and Experimental Neurology
Jingang Li, Tamara Yawno, Amy Sutherland, Jan Loose, Ilias Nitsos, Robert Bischof, Margie Castillo-Melendez, Courtney A McDonald, Flora Y Wong, Graham Jenkin, Suzanne L Miller
Infants born very preterm are at high risk for neurological deficits including cerebral palsy. In this study we assessed the neuroprotective effects of umbilical cord blood cells (UCBCs) and optimal administration timing in a fetal sheep model of preterm brain injury. 50 million allogeneic UCBCs were intravenously administered to fetal sheep (0.7 gestation) at 12h or 5d after acute hypoxia-ischemia (HI) induced by umbilical cord occlusion. The fetal brains were collected at 10d after HI. HI (n=7) was associated with reduced number of oligodendrocytes (Olig2+) and myelin density (CNPase+), and increased density of activated microglia (Iba-1+) in cerebral white matter compared to control fetuses (P<0...
September 2016: Experimental Neurology
Robert Galinsky, Vittoria Draghi, Guido Wassink, Joanne O Davidson, Paul P Drury, Christopher A Lear, Alistair J Gunn, Laura Bennet
Magnesium sulfate is now widely recommended for neuroprotection for preterm birth; however, this has been controversial because there is little evidence that magnesium sulfate is neuroprotective. Preterm fetal sheep (104 days gestation; term is 147 days) were randomly assigned to receive sham occlusion (n = 7), i.v. magnesium sulfate (n = 10) or saline (n = 8) starting 24 h before asphyxia until 24 h after asphyxia. Sheep were killed 72 h after asphyxia. Magnesium sulfate infusion reduced electroencephalograph power and fetal movements before asphyxia...
June 17, 2016: Journal of Cerebral Blood Flow and Metabolism
Reza Mahmoudi, Elham Enant, Hamdollah Delaviz, Parastou Rad, Amrollah Roozbehi, Mehrzad Jafari Barmak, Arsalan Azizi
INTRODUCTION: Prenatal stress has deleterious effects on the development of the brain and is associated with behavioral and psychosocial problems in childhood and adulthood. This study aimed to determine the protective effect of L-arginine on fetal brain under maternal stress. METHODS: Twenty pregnant Wistar rats (weighting 200-230 g) were randomly divided into 4 groups (n=5 for each group). The first nonstress and stress groups received 2 mL of normal saline and the other nonstress and stress two groups received L-arginine (200 mg/kg, IP) from their 5(th) to 20(th) days of pregnancy...
January 2016: Basic and Clinical Neuroscience
Wen-Tung Wang, Phil Lee, Yafeng Dong, Hung-Wen Yeh, Jieun Kim, Carl P Weiner, William M Brooks, In-Young Choi
The guinea pig is a frequently used animal model for human pregnancy complications, such as oxygen deprivation or hypoxia, which result in altered brain development. To investigate the impact of in utero chronic hypoxia on brain development, pregnant guinea pigs underwent either normoxic or hypoxic conditions at about 70 % of 65-day term gestation. After delivery, neurochemical profiles consisting of 19 metabolites and macromolecules were obtained from the neonatal cortex, hippocampus, and striatum from birth to 12 weeks postpartum using in vivo (1)H MR spectroscopy at 9...
July 2016: Neurochemical Research
Ping Zhang, Xuhui Lei, Ying Sun, Haitao Zhang, Liang Chang, Chenlong Li, Daming Liu, Nishant Bhatta, Zhiren Zhang, Chuanlu Jiang
Promoting regenerative repair, including neurogenesis and angiogenesis, may provide a new therapeutic strategy for treatment of stroke. P53, a well-documented transcription factor, has been reported to be involved in cerebral ischemia and also serves as an important regulator of vascular endothelial growth factor (VEGF). However, the role of p53 in endogenous regenerative repair after brain ischemia is poorly understood. In this study, we investigated the effects of PFT-α, a specific p53 inhibitor on neurogenesis and angiogenesis improvement and associated signal pathways in rats impaired by cerebral artery occlusion (MCAo)...
2016: Scientific Reports
Guido Wassink, Joanne O Davidson, Simerdeep K Dhillon, Mhoyra Fraser, Robert Galinsky, Laura Bennet, Alistair J Gunn
Perinatal asphyxia in preterm infants remains a significant contributor to abnormal long-term neurodevelopmental outcomes. Recombinant human erythropoietin has potent non-haematopoietic neuroprotective properties, but there is limited evidence for protection in the preterm brain. Preterm (0.7 gestation) fetal sheep received sham asphyxia (sham occlusion) or asphyxia induced by umbilical cord occlusion for 25 min, followed by an intravenous infusion of vehicle (occlusion-vehicle) or recombinant human erythropoietin (occlusion-Epo, 5000 international units by slow push, then 832...
May 20, 2016: Journal of Cerebral Blood Flow and Metabolism
Laura E McBreairty
Methionine is an essential amino acid which when not incorporated into protein, can be converted to S-adenosylmethionine, the universal methyl donor in over 200 transmethylation reactions, which include creatine and phosphatidylcholine (PC) synthesis, as well as deoxyribonucleic acid (DNA) methylation. Following transmethylation, homocysteine is formed, which can be converted to cysteine via transsulfuration or remethylated to methionine by receiving a methyl group from folate or betaine. Changes to methyl group availability in utero can lead to permanent changes in epigenetic patterns of DNA methylation, which has been implicated in "fetal programming", a phenomenon associated with poor nutrition during fetal development that results in low birth weight and disease in later life...
June 2016: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
Daan R M G Ophelders, Tim G A M Wolfs, Reint K Jellema, Alex Zwanenburg, Peter Andriessen, Tammo Delhaas, Anna-Kristin Ludwig, Stefan Radtke, Vera Peters, Leon Janssen, Bernd Giebel, Boris W Kramer
UNLABELLED: Preterm neonates are susceptible to perinatal hypoxic-ischemic brain injury, for which no treatment is available. In a preclinical animal model of hypoxic-ischemic brain injury in ovine fetuses, we have demonstrated the neuroprotective potential of systemically administered mesenchymal stromal cells (MSCs). The mechanism of MSC treatment is unclear but suggested to be paracrine, through secretion of extracellular vesicles (EVs). Therefore, we investigated in this study the protective effects of mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) in a preclinical model of preterm hypoxic-ischemic brain injury...
June 2016: Stem Cells Translational Medicine
Greer A Bennett, Hannah K Palliser, David Walker, Jonathan Hirst
Prenatal stress has been associated with a variety of developmental changes in offspring, notably those associated with brain development and subsequent risk for neuropathologies later in life. Recently, the importance of the timing and the severity of the stressor during pregnancy has been emphasized with neurosteroids including allopregnanolone implicated in the regulation of stress and also for endogenous neuroprotection in offspring. Prenatal stress was induced using strobe light exposure in pregnant guinea pigs (term 71days) in three defined stress exposure groups (Gestational Age (GA)35-65, GA50-65 and GA60-65)...
August 2016: Psychoneuroendocrinology
M Ohhashi, T Yoshitomi, K Sumiyoshi, Y Kawagoe, S Satoh, H Sameshima, T Ikenoue
OBJECTIVE: Maternal exposure to magnesium sulphate has a neuroprotective effect in premature infants. This study aimed to examine this neuroprotective effect and the dose-response relationship in very-low-birthweight infants born between 24 and 32 weeks of gestation. STUDY DESIGN: A retrospective cohort study compared the rates of mortality and brain damage between three groups: no magnesium sulphate, low-dose (<50g) magnesium sulphate and high-dose (≥50g) magnesium sulphate...
June 2016: European Journal of Obstetrics, Gynecology, and Reproductive Biology
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