TY - JOUR
T1 - The role of the cerebral capillaries in acute ischemic stroke
AU - Østergaard, Leif
AU - Jespersen, Sune Nørhøj
AU - Mouridsen, Kim
AU - Mikkelsen, Irene Klærke
AU - Jonsdottír, Kristjana Ýr
AU - Tietze, Anna
AU - Blicher, Jakob Udby
AU - Aamand, Rasmus
AU - Hjort, Niels
AU - Iversen, Nina Kerting
AU - Cai, Changsi
AU - Hougaard, Kristina Dupont
AU - Simonsen, Claus Z.
AU - Von Weitzel-Mudersbach, Paul
AU - Modrau, Boris
AU - Nagenthiraja, Kartheeban
AU - Riisgaard Ribe, Lars
AU - Hansen, Mikkel Bo
AU - Bekke, Susanne Lise
AU - Dahlman, Martin Gervais
AU - Puig, Josep
AU - Pedraza, Salvador
AU - Serena, Joaquín
AU - Cho, Tae Hee
AU - Siemonsen, Susanne
AU - Thomalla, Götz
AU - Fiehler, Jens
AU - Nighoghossian, Norbert
AU - Andersen, Grethe
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
KW - acute ischemic stroke
KW - capillary transit time heterogeneity (CTTH)
KW - cerebrovascular reserve capacity (CVRC)
KW - penumbra
KW - reperfusion injury
KW - stroke risk factors
U2 - 10.1038/jcbfm.2013.18
DO - 10.1038/jcbfm.2013.18
M3 - Journal article
C2 - 23443173
SN - 0271-678X
VL - 33
SP - 635
EP - 648
JO - Journal of Cerebral Blood Flow and Metabolism
JF - Journal of Cerebral Blood Flow and Metabolism
IS - 5
ER -