title: Regulation of cerebral metabolism during cortical spreading depression.
abstract: We analyzed the metabolic response to cortical spreading depression that drastically increases local energy demand to restore ion homeostasis. During single and multiple cortical spreading depressions in the rat cortex, we simultaneously monitored extracellular levels of glucose and lactate using rapid sampling microdialysis and glucose influx using 18 F-fluorodeoxyglucose positron emission tomography while tracking cortical spreading depression using laser speckle imaging. Combining the acquired data with steady-state requirements we developed a mass-conserving compartment model including neurons and glia that was consistent with the observed data. In summary, our findings are: (1) Early breakdown of glial glycogen provides a major source of energy during increased energy demand and leaves 80% of blood-borne glucose to neurons. (2) Lactate is used solely by neurons and only if extracellular lactate levels are >80% above normal. (3) Although the ratio of oxygen and glucose consumption transiently reaches levels <3, the major part (>90%) of the overall energy supply is from oxidative metabolism. (4) During cortical spreading depression, brain release of lactate exceeds its consumption suggesting that lactate is only a circumstantial energy substrate. Our findings provide a general scenario for the metabolic response to increased cerebral energy demand.
authors.affiliation: Multimodal Imaging of Brain Metabolism, Max Planck Institute for Metabolism Research, Cologne, Germany.
authors.forename: Delphine
authors.initials: D
authors.lastname: Feuerstein
authors.affiliation: Multimodal Imaging of Brain Metabolism, Max Planck Institute for Metabolism Research, Cologne, Germany backes@nf.mpg.de.
authors.forename: Heiko
authors.initials: H
authors.lastname: Backes
authors.affiliation: Multimodal Imaging of Brain Metabolism, Max Planck Institute for Metabolism Research, Cologne, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Gramer
authors.affiliation: Department of Neurosurgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Takagaki
authors.affiliation: Multimodal Imaging of Brain Metabolism, Max Planck Institute for Metabolism Research, Cologne, Germany.
authors.forename: Paula
authors.initials: P
authors.lastname: Gabel
authors.affiliation: Department of Neurosurgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kumagai
authors.affiliation: Multimodal Imaging of Brain Metabolism, Max Planck Institute for Metabolism Research, Cologne, Germany.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Graf
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology; D013181:Cortical Spreading Depression / Q000502:physiology*; D004734:Energy Metabolism; D005947:Glucose / Q000378:metabolism*; D019344:Lactic Acid / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D008959:Models, Neurological; D059906:Neuroimaging; D049268:Positron-Emission Tomography; D017208:Rats, Wistar
chemical_list: D019344:Lactic Acid; D005947:Glucose
keywords: Spreading depression; glucose; glycogen; lactate; positron emission tomography; rapid sampling microdialysis