Inflammatory-induced hibernation in the fetus : priming of fetal sheep metabolism correlates with developmental brain injury
| Autor: | Mark P. Hodson, Hans-Peter Deigner, Hayde Bolouri, David Enot, Carina Mallard, Justin M. Dean, Henrik Hagberg, Matthias Keller, Emeka I. Igwe |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Lipopolysaccharides
Metabolite Medizin lcsh:Medicine Developmental and Pediatric Neurology Pediatrics chemistry.chemical_compound 0302 clinical medicine Pregnancy Hibernation Blood plasma Pathology lcsh:Science 0303 health sciences Multidisciplinary Acute-phase protein Obstetrics and Gynecology Arteries Animal Models 3. Good health Neurology Metabolome Medicine medicine.symptom Research Article medicine.medical_specialty Clinical Research Design Immunology Histopathology Inflammation Brain damage Biology Sepsis 03 medical and health sciences Fetus Model Organisms Developmental Neuroscience Diagnostic Medicine Internal medicine medicine Animals Animal Models of Disease Acute-Phase Reaction 030304 developmental biology Sheep Vital Signs Cerebral Palsy lcsh:R Immunity medicine.disease Pregnancy Complications Endocrinology chemistry Anatomical Pathology Brain Injuries lcsh:Q Clinical Immunology Blood Gas Analysis Neonatology Biomarkers 030217 neurology & neurosurgery Neuroscience General Pathology |
| Zdroj: | PLoS ONE PLoS ONE, Vol 6, Iss 12, p e29503 (2011) |
| Popis: | Prenatal inflammation is considered an important factor contributing to preterm birth and neonatal mortality and morbidity. The impact of prenatal inflammation on fetal bioenergetic status and the correlation of specific metabolites to inflammatory-induced developmental brain injury are unknown. We used a global metabolomics approach to examine plasma metabolites differentially regulated by intrauterine inflammation. Preterm-equivalent sheep fetuses were randomized to i.v. bolus infusion of either saline-vehicle or LPS. Blood samples were collected at baseline 2 h, 6 h and daily up to 10 days for metabolite quantification. Animals were killed at 10 days after LPS injection, and brain injury was assessed by histopathology. We detected both acute and delayed effects of LPS on fetal metabolism, with a long-term down-regulation of fetal energy metabolism. Within the first 3 days after LPS, 121 metabolites were up-regulated or down-regulated. A transient phase (4-6 days), in which metabolite levels recovered to baseline, was followed by a second phase marked by an opposing down-regulation of energy metabolites, increased pO ₂ and increased markers of inflammation and ADMA. The characteristics of the metabolite response to LPS in these two phases, defined as 2 h to 2 days and at 6-9 days, respectively, were strongly correlated with white and grey matter volumes at 10 days recovery. Based on these results we propose a novel concept of inflammatory-induced hibernation of the fetus. Inflammatory priming of fetal metabolism correlated with measures of brain injury, suggesting potential for future biomarker research and the identification of therapeutic targets. © 2011 Keller et al. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|