title: The role of the cerebral capillaries in acute ischemic stroke: the extended penumbra model.
abstract: The pathophysiology of cerebral ischemia is traditionally understood in relation to reductions in cerebral blood flow (CBF). However, a recent reanalysis of the flow-diffusion equation shows that increased capillary transit time heterogeneity (CTTH) can reduce the oxygen extraction efficacy in brain tissue for a given CBF. Changes in capillary morphology are typical of conditions predisposing to stroke and of experimental ischemia. Changes in capillary flow patterns have been observed by direct microscopy in animal models of ischemia and by indirect methods in humans stroke, but their metabolic significance remain unclear. We modeled the effects of progressive increases in CTTH on the way in which brain tissue can secure sufficient oxygen to meet its metabolic needs. Our analysis predicts that as CTTH increases, CBF responses to functional activation and to vasodilators must be suppressed to maintain sufficient tissue oxygenation. Reductions in CBF, increases in CTTH, and combinations thereof can seemingly trigger a critical lack of oxygen in brain tissue, and the restoration of capillary perfusion patterns therefore appears to be crucial for the restoration of the tissue oxygenation after ischemic episodes. In this review, we discuss the possible implications of these findings for the prevention, diagnosis, and treatment of acute stroke.
authors: Department of Neuroradiology, Aarhus University Hospital, Aarhus, Denmark. leif@cfin.dk
authors: Leif
authors: L
authors: Østergaard
authors: Sune Nørhøj
authors: SN
authors: Jespersen
authors: Kim
authors: K
authors: Mouridsen
authors: Irene Klærke
authors: IK
authors: Mikkelsen
authors: Kristjana Ýr
authors: KÝ
authors: Jonsdottír
authors: Anna
authors: A
authors: Tietze
authors: Jakob Udby
authors: JU
authors: Blicher
authors: Rasmus
authors: R
authors: Aamand
authors: Niels
authors: N
authors: Hjort
authors: Nina Kerting
authors: NK
authors: Iversen
authors: Changsi
authors: C
authors: Cai
authors: Kristina Dupont
authors: KD
authors: Hougaard
authors: Claus Z
authors: CZ
authors: Simonsen
authors: Paul
authors: P
authors: Von Weitzel-Mudersbach
authors: Boris
authors: B
authors: Modrau
authors: Kartheeban
authors: K
authors: Nagenthiraja
authors: Lars
authors: L
authors: Riisgaard Ribe
authors: Mikkel Bo
authors: MB
authors: Hansen
authors: Susanne Lise
authors: SL
authors: Bekke
authors: Martin Gervais
authors: MG
authors: Dahlman
authors: Josep
authors: J
authors: Puig
authors: Salvador
authors: S
authors: Pedraza
authors: Joaquín
authors: J
authors: Serena
authors: Tae-Hee
authors: TH
authors: Cho
authors: Susanne
authors: S
authors: Siemonsen
authors: Götz
authors: G
authors: Thomalla
authors: Jens
authors: J
authors: Fiehler
authors: Norbert
authors: N
authors: Nighoghossian
authors: Grethe
authors: G
authors: Andersen
mesh_terms: D000818:Animals; D001921:Brain / Q000098:blood supply* / Q000378:metabolism / Q000503:physiopathology*; D002545:Brain Ischemia / Q000175:diagnosis / Q000378:metabolism / Q000503:physiopathology* / Q000517:prevention & control; D002196:Capillaries / Q000378:metabolism / Q000503:physiopathology*; D002560:Cerebrovascular Circulation; D006801:Humans; D008954:Models, Biological; D010100:Oxygen / Q000378:metabolism; D020521:Stroke / Q000175:diagnosis / Q000378:metabolism / Q000503:physiopathology* / Q000517:prevention & control
chemical_list: D010100:Oxygen