title: Altered hypermetabolic response to cortical spreading depolarizations after traumatic brain injury in rats.
abstract: Spreading depolarizations are waves of near-complete breakdown of neuronal transmembrane ion gradients, free energy starving, and mass depolarization. Spreading depolarizations in electrically inactive tissue are associated with poor outcome in patients with traumatic brain injury. Here, we studied changes in regional cerebral blood flow and brain oxygen (PbtO2), glucose ([Glc]b), and lactate ([Lac]b) concentrations in rats, using minimally invasive real-time sensors. Rats underwent either spreading depolarizations chemically triggered by KCl in naïve cortex in absence of traumatic brain injury or spontaneous spreading depolarizations in the traumatic penumbra after traumatic brain injury, or a cluster of spreading depolarizations triggered chemically by KCl in a remote window from which spreading depolarizations invaded penumbral tissue. Spreading depolarizations in noninjured cortex induced a hypermetabolic response characterized by a decline in [Glc]b and monophasic increases in regional cerebral blood flow, PbtO2, and [Lac]b, indicating transient hyperglycolysis. Following traumatic brain injury, spontaneous spreading depolarizations occurred, causing further decline in [Glc]b and reducing the increase in regional cerebral blood flow and biphasic responses of PbtO2and [Lac]b, followed by prolonged decline. Recovery of PbtO2and [Lac]b was significantly delayed in traumatized animals. Prespreading depolarization [Glc]b levels determined the metabolic response to clusters. The results suggest a compromised hypermetabolic response to spreading depolarizations and slower return to physiological conditions following traumatic brain injury-induced spreading depolarizations.
authors.affiliation: 1 Inserm U1028, CNRS UMR 5292, Lyon Neuroscience Research Center, Team TIGER, Lyon, France.|2 Centre hospitalier universitaire de Lyon, France.
authors.forename: Baptiste
authors.initials: B
authors.lastname: Balança
authors.affiliation: 3 Université Claude Bernard Lyon I, Lyon Neuroscience Research Center, AniRA-Neurochem Technological platform, Lyon, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Meiller
authors.affiliation: 1 Inserm U1028, CNRS UMR 5292, Lyon Neuroscience Research Center, Team TIGER, Lyon, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Bezin
authors.affiliation: 4 Center for Stroke Research Berlin, Charité University Medicine Berlin, Berlin, Germany.|5 Department of Neurology and Department of Experimental Neurology, Charité University Medicine Berlin, Berlin, Germany.
authors.forename: Jens P
authors.initials: JP
authors.lastname: Dreier
authors.affiliation: 1 Inserm U1028, CNRS UMR 5292, Lyon Neuroscience Research Center, Team TIGER, Lyon, France.|3 Université Claude Bernard Lyon I, Lyon Neuroscience Research Center, AniRA-Neurochem Technological platform, Lyon, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Marinesco
authors.affiliation: 1 Inserm U1028, CNRS UMR 5292, Lyon Neuroscience Research Center, Team TIGER, Lyon, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Lieutaud
mesh_terms: D000818:Animals; D001921:Brain / Q000098:blood supply / Q000378:metabolism* / Q000503:physiopathology; D000070642:Brain Injuries, Traumatic / Q000378:metabolism* / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000502:physiology*; D013181:Cortical Spreading Depression / Q000502:physiology*; D004734:Energy Metabolism / Q000502:physiology*; D005947:Glucose / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D010100:Oxygen / Q000378:metabolism; D017208:Rats, Wistar
chemical_list: D019344:Lactic Acid; D005947:Glucose; D010100:Oxygen
keywords: Biosensors; brain metabolism; brain trauma; cerebral blood flow; energy metabolism; spreading depolarization; spreading depression