Perinatal asphyxia as the leading cause of death and brain injury of newborns: prognosis and neuroprotection of
long-term outcomes
• Mario Herrera-Marschitz1• Olga Golubnitchaja2• Diego Bustamante1• Paola Morales1• Verena Klawitter1• Jenny L. Fiedler3
• Micaela Morelli4• Andrew Tasker5• Sonia Gomez-Urquijo6• Tomas Hökfelt7• Michel Goiny8
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 hippo- campus, a concomitant increase of neurogenesis and neurite hyper- trophy 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, prevent- ing 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 peri- natal asphyxia, enlightening the enzyme PARP-1 as a novel target for neuronal protection. The support by FONDECYT, ICBM-En- lace, DAAD-CONICYT Programme-2007 grants is acknowledged.
Corresponding author:
• Prof. Dr. Mario Herrera-Marschitz, University of Chile, Medical Faculty, Programm of Molecular & Clinical Pharmacology, ICBM, Santiago 7, P.O. Box 70.000, Chile
mh-marschitz@med.uchile.cl
1University of Chile, Medical Faculty, Programm of Molecular & Clinical Pharmacology, ICBM, Santiago, Chile
2University of Bonn, Dept. of Experimental Radiology, Bonn, Germany
3University of Chile, Faculty of Chemical and Pharmaceutical Sciences, Department of Biochemistry and Molecular Biology, Laboratory of Neurobiochemistry, Santiago, Chile
4University of Cagliari, Dept. Toxicology, Cagliari, Italy
5University of Prince Edward Island, Department of Biomedical Sciences, Charlottetown, Canada
6University of the Basque Country, Faculty of Medicine, Department of Neuroscience, Spain
7Karolinska Institutet, Dept. of Neuroscience, Stockholm, Schweden
8Karolinska Institutet, Dept. of Physiology & Pharmacology, Stockholm, Schweden
AbstractSpecialareas
©2007 Herrera-Marschitz et al.; licensee GMS Zeitschrift für Medizinische Ausbildung. This is an Open Access article: verbatim copying and redistribution of this article is permitted in all media for any purpose, provided this notice is preserved with the article's original URL.
This article is freely available from http://www.egms.de/en/journals/zma/2007-24/zma000467.shtml
Please cite as: Herrera-Marschitz M, Golubnitchaja O, Bustamante D, Morales P, Klawitter V, Fiedler JL, Morelli M, Tasker A, Gomez-Urquijo S, Hökfelt T, Goiny M. Perinatal asphyxia as the leading cause of death and brain injury of newborns: prognosis and neuroprotection of long-term outcomes. GMS Z Med Ausbild. 2007;24(4):Doc173.
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