title: Monitoring stroke progression: in vivo imaging of cortical perfusion, blood-brain barrier permeability and cellular damage in the rat photothrombosis model.
abstract: Focal cerebral ischemia is among the main causes of death and disability worldwide. The ischemic core often progresses, invading the peri-ischemic brain; however, assessing the propensity of the peri-ischemic brain to undergo secondary damage, understanding the underlying mechanisms, and adjusting treatment accordingly remain clinically unmet challenges. A significant hallmark of the peri-ischemic brain is dysfunction of the blood-brain barrier (BBB), yet the role of disturbed vascular permeability in stroke progression is unclear. Here we describe a longitudinal in vivo fluorescence imaging approach for the evaluation of cortical perfusion, BBB dysfunction, free radical formation and cellular injury using the photothrombosis vascular occlusion model in male Sprague Dawley rats. Blood-brain barrier dysfunction propagated within the peri-ischemic brain in the first hours after photothrombosis and was associated with free radical formation and cellular injury. Inhibiting free radical signaling significantly reduced progressive cellular damage after photothrombosis, with no significant effect on blood flow and BBB permeability. Our approach allows a dynamic follow-up of cellular events and their response to therapeutics in the acutely injured cerebral cortex.
authors.affiliation: Institute for Neurophysiology, Charité-University Medicine Berlin, Berlin, Germany.
authors.forename: Karl
authors.initials: K
authors.lastname: Schoknecht
authors.affiliation: Departments of Physiology and Cell Biology, Cognitive and Brain Sciences, The Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Ofer
authors.initials: O
authors.lastname: Prager
authors.affiliation: Departments of Physiology and Cell Biology, Cognitive and Brain Sciences, The Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Udi
authors.initials: U
authors.lastname: Vazana
authors.affiliation: Departments of Physiology and Cell Biology, Cognitive and Brain Sciences, The Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Lyn
authors.initials: L
authors.lastname: Kamintsky
authors.affiliation: Department of Experimental Neurology, Center for Stroke Research Berlin (CSB), Charité-University Medicine Berlin, Berlin, Germany.
authors.forename: Denise
authors.initials: D
authors.lastname: Harhausen
authors.affiliation: Department of Experimental Neurology, Center for Stroke Research Berlin (CSB), Charité-University Medicine Berlin, Berlin, Germany.
authors.forename: Marietta
authors.initials: M
authors.lastname: Zille
authors.affiliation: Department of Radiology, Charité-University Medicine Berlin, Berlin, Germany.
authors.forename: Lena
authors.initials: L
authors.lastname: Figge
authors.affiliation: Departments of Physiology and Cell Biology, Cognitive and Brain Sciences, The Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Yoash
authors.initials: Y
authors.lastname: Chassidim
authors.affiliation: Department of Radiology, Charité-University Medicine Berlin, Berlin, Germany.
authors.forename: Eyk
authors.initials: E
authors.lastname: Schellenberger
authors.affiliation: Institute for Neurophysiology, Charité-University Medicine Berlin, Berlin, Germany.
authors.forename: Richard
authors.initials: R
authors.lastname: Kovács
authors.affiliation: Institute for Neurophysiology, Charité-University Medicine Berlin, Berlin, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Heinemann
authors.affiliation: 1] Departments of Physiology and Cell Biology, Cognitive and Brain Sciences, The Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, Israel [2] Department of Medical Neuroscience, Faculty of Medicine, Dalhousie University, Halifax, Canada.
authors.forename: Alon
authors.initials: A
authors.lastname: Friedman
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002560:Cerebrovascular Circulation; D004195:Disease Models, Animal; D005609:Free Radicals / Q000378:metabolism; D020767:Intracranial Thrombosis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D010539:Permeability; D051381:Rats; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology
chemical_list: D005609:Free Radicals