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GMS Journal for Medical Education

Gesellschaft für Medizinische Ausbildung (GMA)

ISSN 2366-5017

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Perinatal asphyxia as the leading cause of death and brain injury of newborns: prognosis and neuroprotection of long-term outcomes

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  • corresponding author Mario Herrera-Marschitz - University of Chile, Medical Faculty, Programm of Molecular & Clinical Pharmacology, ICBM, Santiago, Chile
  • author Olga Golubnitchaja - University of Bonn, Dept. of Experimental Radiology, Bonn, Germany
  • author Diego Bustamante - University of Chile, Medical Faculty, Programm of Molecular & Clinical Pharmacology, ICBM, Santiago, Chile
  • author Paola Morales - University of Chile, Medical Faculty, Programm of Molecular & Clinical Pharmacology, ICBM, Santiago, Chile
  • author Verena Klawitter - University of Chile, Medical Faculty, Programm of Molecular & Clinical Pharmacology, ICBM, Santiago, Chile
  • author Jenny L. Fiedler - University of Chile, Chemical and Pharmaceutical Sciences Faculty, Department of Biochemistry and Molecular Biology, Laboratory of Neurobiochemistry, Santiago, Chile
  • author Micaela Morelli - University of Cagliari, Dept. Toxicology, Cagliari, Italy
  • author Andrew Tasker - University of Prince Edward Island, Department of biomedical Sciences, Charlottetown, Canada
  • author Sonia Gomez-Urquijo - University of the Basque Country, Faculty of Medicine, Department of Neuroscience, Spain
  • author Tomas Hökfelt - Karolinska Institutet, Department of Neuroscience, Stockholm, Schweden
  • author Michel Goiny - Karolinska Institutet, Dept. of Physiology & Pharmacology, Stockholm, Schweden

GMS Z Med Ausbild 2007;24(4):Doc173

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/journals/zma/2007-24/zma000467.shtml

Received: September 25, 2007
Revised: September 25, 2007
Accepted: October 1, 2007
Published: November 14, 2007

© 2007 Herrera-Marschitz et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

Abstract

Interruption of oxygen availability and re-oxygenation at birth implies a severe metabolic insult, affecting the development of the central nervous system (CNS), increasing its vulnerability to challenges occurring at adult stages. It has been reported that perinatal asphyxia produces regionally specific neuronal decrease and neurite atrophy in basal ganglia, and hippocampus. In hippocampus, a concomitant increase of neurogenesis and neurite hypertrophy has also been observed. The potential neuroprotection of nicotinamide, a non-selective inhibitor of poly (ADP-ribose) polymerase (PARP-1), has been investigated, finding functional and morphological improvements when administered 24h after the insult (0.8 mmol/kg, i.p., 24, 48 and 72 h after birth.). The main effect of nicotinamide has been seen in neostriatum, preventing an asphyxia-induced decrease of the number of nNOS cells, and nNOS- and dopamine-like neurite atrophy. The present results support the idea that nicotinamide can prevent the effects elicited by a sustained energy-failure condition, as occurring during perinatal asphyxia, enlightening the enzyme PARP-1 as a novel target for neuronal protection. The support by FONDECYT, ICBM-Enlace, DAAD-CONICYT Programme-2007 grants is acknowledged.

Outline

Abstract

Interruption of oxygen availability and re-oxygenation at birth implies a severe metabolic insult, affecting the development of the central nervous system (CNS), increasing its vulnerability to challenges occurring at adult stages. It has been reported that perinatal asphyxia produces regionally specific neuronal decrease and neurite atrophy in basal ganglia, and hippocampus. In hippocampus, a concomitant increase of neurogenesis and neurite hypertrophy has also been observed. The potential neuroprotection of nicotinamide, a non-selective inhibitor of poly (ADP-ribose) polymerase (PARP-1), has been investigated, finding functional and morphological improvements when administered 24h after the insult (0.8 mmol/kg, i.p., 24, 48 and 72 h after birth.). The main effect of nicotinamide has been seen in neostriatum, preventing an asphyxia-induced decrease of the number of nNOS cells, and nNOS- and dopamine-like neurite atrophy. The present results support the idea that nicotinamide can prevent the effects elicited by a sustained energy-failure condition, as occurring during perinatal asphyxia, enlightening the enzyme PARP-1 as a novel target for neuronal protection. The support by FONDECYT, ICBM-Enlace, DAAD-CONICYT Programme-2007 grants is acknowledged.