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MR image-guided investigation of regional signal transducers and activators of transcription-1 activation in a rat model of focal cerebral ischemia

West, DA; Valentim, LM; Lythgoe, MF; Stephanou, A; Proctor, E; Van Der Weerd, L; ... Gadian, DG; + view all (2004) MR image-guided investigation of regional signal transducers and activators of transcription-1 activation in a rat model of focal cerebral ischemia. NEUROSCIENCE , 127 (2) 333 - 339. 10.1016/j.neuroscience.2004.05.022.

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Abstract

Background and purpose: STAT-1 is a member of a family of proteins called signal transducers and activators of transcription (STATs), and recent studies have shown its involvement in the induction of apoptosis. There is limited information on the role of STAT-1 following stroke. In this study we use MRI measurements of cerebral perfusion and bioenergetic status to target measurements of regional STAT-1 activity.Methods: Rats were subjected to 60 or 90 min of middle cerebral artery occlusion with and without reperfusion. MRI maps of the apparent diffusion coefficient of water and cerebral blood flow were acquired throughout the study. After the ischemia or reperfusion period, the brain was excised and samples were analyzed by Western blots using anti-phospho-STAT1 and anti-Fas antibodies. Regions were selected for analysis according to their MRI characteristics.Results: Transcriptional factor STAT-1 was enhanced in the lesion core and, to a lesser extent, in the lesion periphery, following ischemia and reperfusion. This level of activity was greater than for ischemia alone. Western blots demonstrated STAT-1 phosphorylation on tyrosine 701 and not serine 727 after ischemia and 3 h of reperfusion. Enhanced expression of the apoptotic death receptor Fas was confirmed after ischemia followed by reperfusion.Conclusions: This study demonstrates that focal ischemia of the rat brain can induce STAT-1 activation, particularly following a period of reperfusion. The activation occurs not only in the lesion core, but also in the lesion periphery, as identified using MRI. STAT-1 may play an important role in the induction of cell death following stroke. (C) 2004 IBRO. Published by Elsevier Ltd. All rights reserved.

Type:Article
Title:MR image-guided investigation of regional signal transducers and activators of transcription-1 activation in a rat model of focal cerebral ischemia
DOI:10.1016/j.neuroscience.2004.05.022
Keywords:magnetic resonance imaging, stroke, apoptosis, penumbra, diffusion-weighted imaging, APPARENT DIFFUSION-COEFFICIENT, DELAYED NEURONAL DEATH, CELL-DEATH, BLOOD-FLOW, ENERGY-METABOLISM, INDUCED APOPTOSIS, ARTERY OCCLUSION, CYTOCHROME-C, BRAIN, STAT-1
UCL classification:UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Medicine (Division of) > Metabolism and Experimental Therapeutics
UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Child Health > Department of Genes, Development and Disease > ICH - Medical Molecular Biology Unit
UCL > School of BEAMS > Faculty of Engineering Science > Medical Physics and Bioengineering

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