Abstract | INTRODUCTION: To implement neuroprotective strategies in newborns, sensitive and specific biomarkers are needed for identifying those who are at risk for brain damage. We evaluated the effectiveness of matrix metalloproteinases ( MMPs) and their naturally occurring tissue inhibitors of metalloproteinases (TIMPs) in predicting neonatal encephalopathy (NE) damage in newborns. RESULTS: Plasma MMP-9 and TIMP-1 levels were upregulated as early as 1 h after the HI insult but not did not show such elevations after other types of injury (ibotenate-induced excitotoxicity, hypoxia, lipopolysaccharide-induced inflammation), and brain levels reflected this increase soon thereafter. We confirmed these results by carrying out plasma MMP-9 and TIMP-1 measurements in human newborns with NE. In these infants, protein levels of MMP-9 and TIMP-1 were found to be elevated during a short window up to 6 h after birth. DISCUSSION: This feature is particularly useful in identifying newborns in need of neuroprotection. A second peak observed 72 h after birth is possibly related to the second phase of energy failure after a HI insult. Our data, although preliminary, support the use of MMP-9 and TIMP-1 as early biomarkers for the presence and extent of perinatal brain injury in human term newborns. METHODS: We first used a mouse model of neonatal HI injury to explore mechanistic aspects such as the time course of these markers after the hypoxia- ischemia event, and the correlation between the levels of these candidate markers in brain and plasma.
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Authors | Nathalie Bednarek, Pernilla Svedin, Roselyne Garnotel, Géraldine Favrais, Gauthier Loron, Leslie Schwendiman, Henrik Hagberg, Patrice Morville, Carina Mallard, Pierre Gressens |
Journal | Pediatric research
(Pediatr Res)
Vol. 71
Issue 1
Pg. 63-70
(Jan 2012)
ISSN: 1530-0447 [Electronic] United States |
PMID | 22289852
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Biomarkers
- Tissue Inhibitor of Metalloproteinase-1
- Matrix Metalloproteinase 9
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Topics |
- Animals
- Animals, Newborn
- Biomarkers
(metabolism)
- Brain
(metabolism, pathology)
- Female
- Gestational Age
- Humans
- Hypoxia-Ischemia, Brain
(pathology, physiopathology)
- Infant, Newborn
- Infant, Newborn, Diseases
(pathology, physiopathology)
- Male
- Matrix Metalloproteinase 9
(blood)
- Mice
- Mice, Inbred C57BL
- Tissue Inhibitor of Metalloproteinase-1
(blood)
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