Resuscitation of newborn piglets. short-term influence of FiO2 on matrix metalloproteinases, caspase-3 and BDNF

• Published in: PloS one 2010-12, Vol.5 (12), p.e14261
• Main Authors: Solberg, Rønnaug, Løberg, Else Marit, Andresen, Jannicke H, Wright, Marianne S, Charrat, Eliane, Khrestchatisky, Michel, Rivera, Santiago, Saugstad, Ola Didrik
• Format: Article
• Language: English
• Subjects: Animals; Animals, Newborn; Apoptosis; Brain; Brain damage; Brain injury; Brain research; Brain-derived neurotrophic factor; Brain-Derived Neurotrophic Factor - biosynthesis; Caspase; Caspase 3 - biosynthesis; Caspase-3; Cell Death; Cerebellum - metabolism; Cerebral Cortex - metabolism; Cloning; Corpus striatum; Corpus Striatum - metabolism; Cortex (frontal); Critical Care and Emergency Medicine; Gene expression; Gene regulation; Hemispheric laterality; Hippocampus - metabolism; Histopathology; Hyperoxia; Hypoxia; Immunohistochemistry; Immunology/Genetics of the Immune System; Ischemia; Matrix metalloproteinase; Matrix metalloproteinases; Matrix Metalloproteinases - biosynthesis; Metalloproteinase; Morbidity; Neostriatum; Neurodegeneration; Neuroprotection; Neuroscience/Neurodevelopment; Neurotoxicity; Oxidation; Oxygen; Oxygen - chemistry; Oxygen - metabolism; Oxygen - therapeutic use; Pediatrics and Child Health/Neonatology; Pediatrics and Child Health/Pediatric Critical Care; Proteolysis; Resuscitation; Resuscitation - methods; Swine; Time Factors; Trends
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0014261

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. 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