title: Capillary transit time heterogeneity and flow-metabolism coupling after traumatic brain injury.
abstract: Most patients who die after traumatic brain injury (TBI) show evidence of ischemic brain damage. Nevertheless, it has proven difficult to demonstrate cerebral ischemia in TBI patients. After TBI, both global and localized changes in cerebral blood flow (CBF) are observed, depending on the extent of diffuse brain swelling and the size and location of contusions and hematoma. These changes vary considerably over time, with most TBI patients showing reduced CBF during the first 12 hours after injury, then hyperperfusion, and in some patients vasospasms before CBF eventually normalizes. This apparent neurovascular uncoupling has been ascribed to mitochondrial dysfunction, hindered oxygen diffusion into tissue, or microthrombosis. Capillary compression by astrocytic endfeet swelling is observed in biopsies acquired from TBI patients. In animal models, elevated intracranial pressure compresses capillaries, causing redistribution of capillary flows into patterns argued to cause functional shunting of oxygenated blood through the capillary bed. We used a biophysical model of oxygen transport in tissue to examine how capillary flow disturbances may contribute to the profound changes in CBF after TBI. The analysis suggests that elevated capillary transit time heterogeneity can cause critical reductions in oxygen availability in the absence of 'classic' ischemia. We discuss diagnostic and therapeutic consequences of these predictions.
authors: 1] Department of Neuroradiology, Aarhus University Hospital, Aarhus, Denmark [2] Center of Functionally Integrative Neuroscience and MINDLab, Aarhus University, Aarhus, Denmark.
authors: Leif
authors: L
authors: Østergaard
authors: Center of Functionally Integrative Neuroscience and MINDLab, Aarhus University, Aarhus, Denmark.
authors: Thorbjørn S
authors: TS
authors: Engedal
authors: Center of Functionally Integrative Neuroscience and MINDLab, Aarhus University, Aarhus, Denmark.
authors: Rasmus
authors: R
authors: Aamand
authors: Department of Neuroradiology, Aarhus University Hospital, Aarhus, Denmark.
authors: Ronni
authors: R
authors: Mikkelsen
authors: Center of Functionally Integrative Neuroscience and MINDLab, Aarhus University, Aarhus, Denmark.
authors: Nina K
authors: NK
authors: Iversen
authors: Center of Functionally Integrative Neuroscience and MINDLab, Aarhus University, Aarhus, Denmark.
authors: Maryam
authors: M
authors: Anzabi
authors: Hammel Neurorehabilitation Hospital, Hammel, Denmark.
authors: Erhard T
authors: ET
authors: Næss-Schmidt
authors: Center of Functionally Integrative Neuroscience and MINDLab, Aarhus University, Aarhus, Denmark.
authors: Kim R
authors: KR
authors: Drasbek
authors: Center of Functionally Integrative Neuroscience and MINDLab, Aarhus University, Aarhus, Denmark.
authors: Vibeke
authors: V
authors: Bay
authors: 1] Center of Functionally Integrative Neuroscience and MINDLab, Aarhus University, Aarhus, Denmark [2] Hammel Neurorehabilitation Hospital, Hammel, Denmark.
authors: Jakob U
authors: JU
authors: Blicher
authors: 1] Department of Neuroradiology, Aarhus University Hospital, Aarhus, Denmark [2] Center of Functionally Integrative Neuroscience and MINDLab, Aarhus University, Aarhus, Denmark.
authors: Anna
authors: A
authors: Tietze
authors: Center of Functionally Integrative Neuroscience and MINDLab, Aarhus University, Aarhus, Denmark.
authors: Irene K
authors: IK
authors: Mikkelsen
authors: Center of Functionally Integrative Neuroscience and MINDLab, Aarhus University, Aarhus, Denmark.
authors: Brian
authors: B
authors: Hansen
authors: Center of Functionally Integrative Neuroscience and MINDLab, Aarhus University, Aarhus, Denmark.
authors: Sune N
authors: SN
authors: Jespersen
authors: Department of Anesthesiology and Critical Care Medicine, Aarhus University Hospital, Aarhus, Denmark.
authors: Niels
authors: N
authors: Juul
authors: Department of Neurosurgery, Aarhus University Hospital, Aarhus, Denmark.
authors: Jens C H
authors: JC
authors: Sørensen
authors: Department of Anesthesiology and Critical Care Medicine, Aarhus University Hospital, Aarhus, Denmark.
authors: Mads
authors: M
authors: Rasmussen
mesh_terms: D000818:Animals; D001921:Brain / Q000098:blood supply* / Q000378:metabolism / Q000503:physiopathology; D001930:Brain Injuries / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology*; D002196:Capillaries / Q000378:metabolism / Q000503:physiopathology*; D002560:Cerebrovascular Circulation; D005947:Glucose / Q000378:metabolism; D006439:Hemodynamics; D006801:Humans; D010100:Oxygen / Q000378:metabolism; D020286:Pericytes / Q000378:metabolism / Q000473:pathology
chemical_list: D005947:Glucose; D010100:Oxygen