Document Detail


Resuscitation of newborn piglets. short-term influence of FiO2 on matrix metalloproteinases, caspase-3 and BDNF.
MedLine Citation:
PMID:  21151608     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Perinatal hypoxia-ischemia is a major cause of mortality and cerebral morbidity, and using oxygen during newborn resuscitation may further harm the brain. The aim was to examine how supplementary oxygen used for newborn resuscitation would influence early brain tissue injury, cell death and repair processes and the regulation of genes related to apoptosis, neurodegeneration and neuroprotection.
METHODS AND FINDINGS: Anesthetized newborn piglets were subjected to global hypoxia and then randomly assigned to resuscitation with 21%, 40% or 100% O(2) for 30 min and followed for 9 h. An additional group received 100% O(2) for 30 min without preceding hypoxia. The left hemisphere was used for histopathology and immunohistochemistry and the right hemisphere was used for in situ zymography in the corpus striatum; gene expression and the activity of various relevant biofactors were measured in the frontal cortex. There was an increase in the net matrix metalloproteinase gelatinolytic activity in the corpus striatum from piglets resuscitated with 100% oxygen vs. 21%. Hematoxylin-eosin (HE) staining revealed no significant changes. Nine hours after oxygen-assisted resuscitation, caspase-3 expression and activity was increased by 30-40% in the 100% O(2) group (n = 9/10) vs. the 21% O(2) group (n = 10; p<0.04), whereas brain-derived neurotrophic factor (BDNF) activity was decreased by 65% p<0.03.
CONCLUSIONS: The use of 100% oxygen for resuscitation resulted in increased potentially harmful proteolytic activities and attenuated BDNF activity when compared with 21%. Although there were no significant changes in short term cell loss, hyperoxia seems to cause an early imbalance between neuroprotective and neurotoxic mechanisms that might compromise the final pathological outcome.
Authors:
Rønnaug Solberg; Else Marit Løberg; Jannicke H Andresen; Marianne S Wright; Eliane Charrat; Michel Khrestchatisky; Santiago Rivera; Ola Didrik Saugstad
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-12-09
Journal Detail:
Title:  PloS one     Volume:  5     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2010  
Date Detail:
Created Date:  2010-12-14     Completed Date:  2011-07-05     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e14261     Citation Subset:  IM    
Affiliation:
Department of Paediatric Research, University of Oslo and Oslo University Hospital, Rikshospitalet, Oslo, Norway. ronnaug.solberg@medisin.uio.no
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MeSH Terms
Descriptor/Qualifier:
Animals
Animals, Newborn
Apoptosis
Brain-Derived Neurotrophic Factor / biosynthesis*
Caspase 3 / biosynthesis*
Cell Death
Cerebellum / metabolism
Cerebral Cortex / metabolism
Corpus Striatum / metabolism
Hippocampus / metabolism
Matrix Metalloproteinases / biosynthesis*
Oxygen / chemistry,  metabolism*,  therapeutic use
Resuscitation / methods*
Swine
Time Factors
Chemical
Reg. No./Substance:
0/Brain-Derived Neurotrophic Factor; 7782-44-7/Oxygen; EC 3.4.22.-/Caspase 3; EC 3.4.24.-/Matrix Metalloproteinases
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