title: Fetal asphyxia induces acute and persisting changes in the ceramide metabolism in rat brain.
abstract: Fetal asphyctic preconditioning, induced by a brief episode of experimental hypoxia-ischemia, offers neuroprotection to a subsequent more severe asphyctic insult at birth. Extensive cell stress and apoptosis are important contributing factors of damage in the asphyctic neonatal brain. Because ceramide acts as a second messenger for multiple apoptotic stimuli, including hypoxia/ischemia, we sought to investigate the possible involvement of the ceramide pathway in endogenous neuroprotection induced by fetal asphyctic preconditioning. Global fetal asphyxia was induced in rats by clamping both uterine and ovarian vasculature for 30 min. Fetal asphyxia resulted in acute changes in brain ceramide/sphingomyelin metabolic enzymes, ceramide synthase 1, 2, and 5, acid sphingomyelinase, sphingosine-1-phosphate phosphatase, and the ceramide transporter. This observation correlated with an increase in neuronal apoptosis and in astrocyte number. After birth, ceramide and sphingomyelin levels remained high in fetal asphyxia brains, suggesting that a long-term regulation of the ceramide pathway may be involved in the mechanism of tolerance to a subsequent, otherwise lethal, asphyctic event.
authors.affiliation: Department of Neuroscience, Maastricht University, School of Mental Health and Neuroscience (MHeNS), Maastricht, The Netherlands.
authors.forename: Evi
authors.initials: E
authors.lastname: Vlassaks
authors.forename: Chiara
authors.initials: C
authors.lastname: Mencarelli
authors.forename: Maria
authors.initials: M
authors.lastname: Nikiforou
authors.forename: Eveline
authors.initials: E
authors.lastname: Strackx
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Ferraz
authors.forename: Johannes M
authors.initials: JM
authors.lastname: Aerts
authors.forename: Marc H
authors.initials: MH
authors.lastname: De Baets
authors.forename: Pilar
authors.initials: P
authors.lastname: Martinez-Martinez
authors.forename: Antonio W D
authors.initials: AW
authors.lastname: Gavilanes
mesh_terms: D000818:Animals; D001237:Asphyxia / Q000378:metabolism*; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002518:Ceramides / Q000378:metabolism*; D005260:Female; D005311:Fetal Hypoxia / Q000378:metabolism*; D011247:Pregnancy; D011270:Pregnancy, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley; D013109:Sphingomyelins / Q000378:metabolism
chemical_list: D002518:Ceramides; D013109:Sphingomyelins
keywords: apoptosis; inflammation; neonatal rat; neuroprotection; sphingomyelin