title: Neurovascular coupling in rat brain operates independent of hemoglobin deoxygenation.
abstract: Recently, a universal, simple, and fail-safe mechanism has been proposed by which cerebral blood flow (CBF) might be coupled to oxygen metabolism during neuronal activation without the need for any tissue-based mechanism. According to this concept, vasodilation occurs by local erythrocytic release of nitric oxide or ATP wherever and whenever hemoglobin is deoxygenated, directly matching oxygen demand and supply in every tissue. For neurovascular coupling in the brain, we present experimental evidence challenging this view by applying an experimental regime operating without deoxy-hemoglobin. Hyperbaric hyperoxygenation (HBO) allowed us to prevent hemoglobin deoxygenation, as the oxygen that was physically dissolved in the tissue was sufficient to support oxidative metabolism. Regional CBF and regional cerebral blood oxygenation were measured using a cranial window preparation in anesthetized rats. Hemodynamic and neuronal responses to electrical forepaw stimulation or cortical spreading depression (CSD) were analyzed under normobaric normoxia and during HBO up to 4 ATA (standard atmospheres absolute). Inconsistent with the proposed mechanism, during HBO, CBF responses to functional activation or CSD were unchanged. Our results show that activation-induced CBF regulation in the brain does not operate through the release of vasoactive mediators on hemoglobin deoxygenation or through a tissue-based oxygen-sensing mechanism.
authors.affiliation: Departments of Neurology and Experimental Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany. ute.lindauer@lrz.tum.de
authors.forename: Ute
authors.initials: U
authors.lastname: Lindauer
authors.forename: Christoph
authors.initials: C
authors.lastname: Leithner
authors.forename: Heike
authors.initials: H
authors.lastname: Kaasch
authors.forename: Benjamin
authors.initials: B
authors.lastname: Rohrer
authors.forename: Marco
authors.initials: M
authors.lastname: Foddis
authors.forename: Martina
authors.initials: M
authors.lastname: Füchtemeier
authors.forename: Nikolas
authors.initials: N
authors.lastname: Offenhauser
authors.forename: Jens
authors.initials: J
authors.lastname: Steinbrink
authors.forename: Georg
authors.initials: G
authors.lastname: Royl
authors.forename: Matthias
authors.initials: M
authors.lastname: Kohl-Bareis
authors.forename: Ulrich
authors.initials: U
authors.lastname: Dirnagl
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D002560:Cerebrovascular Circulation / Q000502:physiology*; D013181:Cortical Spreading Depression / Q000502:physiology; D006439:Hemodynamics; D006454:Hemoglobins / Q000378:metabolism*; D006931:Hyperbaric Oxygenation; D008297:Male; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D010101:Oxygen Consumption / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000502:physiology*; D014661:Vasoconstriction / Q000502:physiology
chemical_list: D006454:Hemoglobins; D009569:Nitric Oxide; D010100:Oxygen