title: Prostaglandin E2 metabolism in rat brain: Role of the blood-brain interfaces.
abstract: BACKGROUND
  Prostaglandin E2 (PGE2) is involved in the regulation of synaptic activity and plasticity, and in brain maturation. It is also an important mediator of the central response to inflammatory challenges. The aim of this study was to evaluate the ability of the tissues forming the blood-brain interfaces to act as signal termination sites for PGE2 by metabolic inactivation.
  
  
  METHODS
  The specific activity of 15-hydroxyprostaglandin dehydrogenase was measured in homogenates of microvessels, choroid plexuses and cerebral cortex isolated from postnatal and adult rat brain, and compared to the activity measured in peripheral organs which are established signal termination sites for prostaglandins. PGE2 metabolites produced ex vivo by choroid plexuses were identified and quantified by HPLC coupled to radiochemical detection.
  
  
  RESULTS
  The data confirmed the absence of metabolic activity in brain parenchyma, and showed that no detectable activity was associated with brain microvessels forming the blood-brain barrier. By contrast, 15-hydroxyprostaglandin dehydrogenase activity was measured in both fourth and lateral ventricle choroid plexuses from 2-day-old rats, albeit at a lower level than in lung or kidney. The activity was barely detectable in adult choroidal tissue. Metabolic profiles indicated that isolated choroid plexus has the ability to metabolize PGE2, mainly into 13,14-dihydro-15-keto-PGE2. In short-term incubations, this metabolite distributed in the tissue rather than in the external medium, suggesting its release in the choroidal stroma.
  
  
  CONCLUSIONS
  The rat choroidal tissue has a significant ability to metabolize PGE2 during early postnatal life. This metabolic activity may participate in signal termination of centrally released PGE2 in the brain, or function as an enzymatic barrier acting to maintain PGE2 homeostasis in CSF during the critical early postnatal period of brain development.
authors.affiliation: INSERM, U 842, Lyon; Université de Lyon; Faculté de médecine Laennec, UMR-S842, Lyon, F69372, France. ghersi-egea@lyon.inserm.fr.
authors.forename: Eudeline
authors.initials: E
authors.lastname: Alix
authors.forename: Charlotte
authors.initials: C
authors.lastname: Schmitt
authors.forename: Nathalie
authors.initials: N
authors.lastname: Strazielle
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Ghersi-Egea