title: Ischemia-induced depolarizations and associated hemodynamic responses in incomplete global forebrain ischemia in rats.
abstract: Spontaneous depolarizations around the core are a consistent feature of focal cerebral ischemia, but the associated regional hemodynamic changes are heterogeneous. We determined how the features of depolarizations relate to subsequent cerebral blood flow (CBF) changes in global forebrain ischemia. Forebrain ischemia was produced in halothane-anesthetized rats (n=13) by common carotid artery occlusion and hypovolemic hypotension. Mean arterial blood pressure (MABP) was monitored via a femoral catheter. Specific illuminations allowed the capture of image sequences through a cranial window to visualize: changes in membrane potential (voltage-sensitive dye method); CBF (laser speckle contrast imaging); cerebral blood volume (intrinsic optical signal, IOS at 540-550nm); and hemoglobin deoxygenation (IOS at 620-640nm). A depolarization occurred (n=9) when CBF fell below 43.4±5% of control (41±4mmHg MABP), and propagated with a distinct wave front at a rate of 2.8mm/min. Depolarizations were either persistent (n=4), intermediate (n=3) or short, transient depolarization (n=2). Persistent and intermediate depolarizations were associated with sustained hypoperfusion (-11.7±5.1%) and transient hypoperfusion (-17.4±5.2, relative to CBF before depolarization). Short, transient depolarizations did not generate clear CBF responses. Depolarizations during incomplete global ischemia occurred at the lower limit of CBF autoregulation, propagated similar to spreading depolarization (SD), and the hemodynamic responses indicated inverse neurovascular coupling. Similar to SDs associated with focal stroke, the propagating event can be persistent or transient.
authors.affiliation: Department of Medical Physics and Informatics, Faculty of Medicine, University of Szeged, H-6720 Szeged, Korányi fasor 9, Hungary; Department of Physiology, Faculty of Medicine, University of Szeged, H-6720 Szeged, Dóm tér 10, Hungary. Electronic address: berezsofia@gmail.com.
authors.forename: Z
authors.initials: Z
authors.lastname: Bere
authors.affiliation: Department of Medical Physics and Informatics, Faculty of Medicine, University of Szeged, H-6720 Szeged, Korányi fasor 9, Hungary. Electronic address: t.obrenovitch@live.fr.
authors.forename: T P
authors.initials: TP
authors.lastname: Obrenovitch
authors.affiliation: Department of Medical Physics and Informatics, Faculty of Medicine, University of Szeged, H-6720 Szeged, Korányi fasor 9, Hungary. Electronic address: bari.ferenc@med.u-szeged.hu.
authors.forename: F
authors.initials: F
authors.lastname: Bari
authors.affiliation: Department of Medical Physics and Informatics, Faculty of Medicine, University of Szeged, H-6720 Szeged, Korányi fasor 9, Hungary; Department of Physiology, Faculty of Medicine, University of Szeged, H-6720 Szeged, Dóm tér 10, Hungary. Electronic address: eszter.farkas.szeged@gmail.com.
authors.forename: E
authors.initials: E
authors.lastname: Farkas
mesh_terms: D000818:Animals; D062186:Arterial Pressure; D002545:Brain Ischemia / Q000503:physiopathology*; D002540:Cerebral Cortex / Q000098:blood supply* / Q000503:physiopathology*; D006439:Hemodynamics; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
keywords: 2VO; ANOVA; AOI; CBF; CBV; GR; Hb; IID; IOS; LSC; MABP; MCAO; PID; RD; SD; VS; aCSF; analysis of variance; area of interest; artificial cerebrospinal fluid; bilateral occlusion of the common carotid arteries (two-vessel occlusion); cerebral blood flow; cerebral blood volume; gl; global ischemia; gray level; green; hemoglobin; imaging; intrinsic optical signal; ischemia-induced depolarization; laser speckle contrast; mean arterial blood pressure; middle cerebral artery occlusion; neurovascular coupling; peri-infarct depolarization; red; spreading depolarization; voltage sensitive