title: Circulating bacterial lipopolysaccharide-induced inflammation reduces flow in brain-irrigating arteries independently from cerebrovascular prostaglandin production.
abstract: Brain dysfunction is a frequent complication of the systemic inflammatory response to bacterial infection or sepsis. In the present work, the effects of intravenous bacterial lipopolysaccharide (LPS) administration on cerebral arterial blood flow were assessed with time-of-flight (TOF)-based magnetic resonance angiography (MRA) in mice. Cerebral expression of the transcription factors nuclear factor-kappaB (NF-κB) and c-Fos and that of enzymes synthesizing vasoactive mediators, such as prostaglandins and nitric oxide, known to be increased under inflammatory conditions, were studied in the same animals. Time-resolved TOF MRA revealed no differences in blood flow in the internal carotids upstream of the circle of Willis, but indicated lower flow in its lateral parts as well as in the middle and anterior cerebral arteries after intravenous LPS injection as compared to saline administration. Although LPS did not increase c-Fos expression in ventral forebrain structures of these animals, it did induce NF-κB in meningeal blood vessels. LPS also increased cerebral expression of cyclooxygenase-2 and prostaglandin E synthase mRNAs, but de novo expression occurred in veins rather than in arteries. In conclusion, our work indicates that LPS-induced systemic inflammation does not necessarily affect filling of the circle of the Willis from the periphery, but that circulating LPS alters outflow from the circle of Willis to the middle and anterior cerebral arteries. These modifications in arterial flow were not related to increased cerebral synthesis of prostaglandins, but may instead be the consequence of the action of circulating prostaglandins and other vasoactive mediators on brain-irrigating arteries during systemic inflammation.
authors.affiliation: Service de Neuropédiatrie, CIC-0005, Centre Hospitalier Universitaire (CHU) de Bordeaux, Bordeaux, France; CNRS, Résonance Magnétique des Systèmes Biologiques, UMR 5536, Bordeaux, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Villéga
authors.affiliation: Univ. Bordeaux, RMSB, UMR 5536, Bordeaux, France; CNRS, PsychoNeuroImmunologie, Nutrition et Génétique, UMR 5226, Bordeaux, France.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Delpech
authors.affiliation: CNRS, Résonance Magnétique des Systèmes Biologiques, UMR 5536, Bordeaux, France; Univ. Bordeaux, RMSB, UMR 5536, Bordeaux, France; Service de Anesthésie Réanimation Neurochirurgicale, Centre Hospitalier Universitaire (CHU) de Bordeaux, Bordeaux, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Griton
authors.affiliation: Univ. Bordeaux, RMSB, UMR 5536, Bordeaux, France; CNRS, PsychoNeuroImmunologie, Nutrition et Génétique, UMR 5226, Bordeaux, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: André
authors.affiliation: CNRS, Résonance Magnétique des Systèmes Biologiques, UMR 5536, Bordeaux, France; Univ. Bordeaux, RMSB, UMR 5536, Bordeaux, France.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Franconi
authors.affiliation: CNRS, Résonance Magnétique des Systèmes Biologiques, UMR 5536, Bordeaux, France; Univ. Bordeaux, RMSB, UMR 5536, Bordeaux, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Miraux
authors.affiliation: CNRS, Résonance Magnétique des Systèmes Biologiques, UMR 5536, Bordeaux, France; Univ. Bordeaux, RMSB, UMR 5536, Bordeaux, France. Electronic address: jan-pieter.konsman@u-bordeaux.fr.
authors.forename: Jan Pieter
authors.initials: JP
authors.lastname: Konsman
mesh_terms: D000818:Animals; D002536:Cerebral Arteries / Q000382:microbiology / Q000503:physiopathology*; D002540:Cerebral Cortex / Q000098:blood supply / Q000378:metabolism* / Q000382:microbiology / Q000503:physiopathology*; D051546:Cyclooxygenase 2; D007249:Inflammation / Q000378:metabolism / Q000503:physiopathology*; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D018810:Magnetic Resonance Angiography; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; D016328:NF-kappa B; D011453:Prostaglandins; D016760:Proto-Oncogene Proteins c-fos; C002744:3-nitrotyrosine; D014443:Tyrosine; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2
keywords: angiography; anterior cerebral artery; cerebral blood flow; encephalopathy; prostaglandin; sepsis