title: Glucose consumption of inflammatory cells masks metabolic deficits in the brain.
abstract: Inflammatory cells such as microglia need energy to exert their functions and to maintain their cellular integrity and membrane potential. Subsequent to cerebral ischemia, inflammatory cells infiltrate tissue with limited blood flow where neurons and astrocytes died due to insufficient supply with oxygen and glucose. Using dual tracer positron emission tomography (PET), we found that concomitant with the presence of inflammatory cells, transport and consumption of glucose increased up to normal levels but returned to pathological levels as soon as inflammatory cells disappeared. Thus, inflammatory cells established sufficient glucose supply to satisfy their energy demands even in regions with insufficient supply for neurons and astrocytes to survive. Our data suggest that neurons and astrocytes died from oxygen deficiency and inflammatory cells metabolized glucose non-oxidatively in regions with residual availability. As a consequence, glucose metabolism of inflammatory cells can mask metabolic deficits in neurodegenerative diseases. We further found that the PET tracer did not bind to inflammatory cells in severely hypoperfused regions and thus only a part of the inflammation was detected. We conclude that glucose consumption of inflammatory cells should be taken into account when analyzing disease-related alterations of local cerebral metabolism.
authors.affiliation: Max Planck Institute for Metabolism Research, Cologne, Germany. Electronic address: backes@sf.mpg.de.
authors.forename: Heiko
authors.initials: H
authors.lastname: Backes
authors.affiliation: Max Planck Institute for Metabolism Research, Cologne, Germany; Department of Neurology, University Hospital, Cologne, Germany.
authors.forename: Maureen
authors.initials: M
authors.lastname: Walberer
authors.affiliation: Max Planck Institute for Metabolism Research, Cologne, Germany; Department of Neurology, University Hospital, Cologne, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Ladwig
authors.affiliation: Max Planck Institute for Metabolism Research, Cologne, Germany; Department of Neurology, University Hospital, Cologne, Germany.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Rueger
authors.affiliation: Max Planck Institute for Metabolism Research, Cologne, Germany; Department of Radiochemistry and Experimental Molecular Imaging, University of Cologne, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Neumaier
authors.affiliation: Department of Radiochemistry and Experimental Molecular Imaging, University of Cologne, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Endepols
authors.affiliation: Max Planck Institute for Metabolism Research, Cologne, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Hoehn
authors.affiliation: Department of Neurology, University Hospital, Cologne, Germany; Institute of Neuroscience and Medicine (INM-3), Cognitive Neurology Section, Research Centre Juelich, Germany.
authors.forename: Gereon R
authors.initials: GR
authors.lastname: Fink
authors.affiliation: Max Planck Institute for Metabolism Research, Cologne, Germany; Department of Neurology, University Hospital, Cologne, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Schroeter
authors.affiliation: Max Planck Institute for Metabolism Research, Cologne, Germany.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Graf
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002545:Brain Ischemia / Q000378:metabolism*; D004734:Energy Metabolism / Q000502:physiology*; D005947:Glucose / Q000378:metabolism*; D007091:Image Processing, Computer-Assisted; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D049268:Positron-Emission Tomography; D051381:Rats; D017208:Rats, Wistar
chemical_list: D005947:Glucose
keywords: Cerebral ischemia; FDG; Glucose metabolism; Neuroinflammation; Positron emission tomography; [(11)C]PK11195