title: Single-cell resolution mapping of neuronal damage in acute focal cerebral ischemia using thallium autometallography.
abstract: Neuronal damage shortly after onset or after brief episodes of cerebral ischemia has remained difficult to assess with clinical and preclinical imaging techniques as well as with microscopical methods. We here show, in rodent models of middle cerebral artery occlusion (MCAO), that neuronal damage in acute focal cerebral ischemia can be mapped with single-cell resolution using thallium autometallography (TlAMG), a histochemical technique for the detection of the K(+)-probe thallium (Tl(+)) in the brain. We intravenously injected rats and mice with thallium diethyldithiocarbamate (TlDDC), a lipophilic chelate complex that releases Tl(+) after crossing the blood-brain barrier. We found, within the territories of the affected arteries, areas of markedly reduced neuronal Tl(+) uptake in all animals at all time points studied ranging from 15 minutes to 24 hours after MCAO. In large lesions at early time points, areas with neuronal and astrocytic Tl(+) uptake below thresholds of detection were surrounded by putative penumbral zones with preserved but diminished Tl(+) uptake. At 24 hours, the areas of reduced Tl(+)uptake matched with areas delineated by established markers of neuronal damage. The results suggest the use of (201)TlDDC for preclinical and clinical single-photon emission computed tomography (SPECT) imaging of hyperacute alterations in brain K(+) metabolism and prediction of tissue viability in cerebral ischemia.
authors.affiliation: 1] Department of Experimental Neurology, Center for Stroke Research Berlin (CSB), Charité-University Medicine Berlin, Berlin, Germany [2] Department of Auditory Learning and Speech, Leibniz Institute for Neurobiology, Magdeburg, Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Stöber
authors.affiliation: 1] Project Group Neuropharmacology, Leibniz Institute for Neurobiology, Magdeburg, Germany [2] German Center for Neurodegenerative Diseases (DZNE), Partner site Magdeburg, Magdeburg, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Baldauf
authors.affiliation: 1] Project Group Neuropharmacology, Leibniz Institute for Neurobiology, Magdeburg, Germany [2] Research Institute for Applied Neurosciences (FAN) GmbH, Magdeburg, Germany [3] Institute of Health & Society, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Iryna
authors.initials: I
authors.lastname: Ziabreva
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: 1] Department of Auditory Learning and Speech, Leibniz Institute for Neurobiology, Magdeburg, Germany [2] Institute of Cell Biology and Neurobiology, Charité-University Medicine Berlin, Berlin, Germany.
authors.forename: Jenni
authors.initials: J
authors.lastname: Neubert
authors.affiliation: 1] Project Group Neuropharmacology, Leibniz Institute for Neurobiology, Magdeburg, Germany [2] German Center for Neurodegenerative Diseases (DZNE), Partner site Magdeburg, Magdeburg, Germany.
authors.forename: Klaus G
authors.initials: KG
authors.lastname: Reymann
authors.affiliation: 1] Department of Auditory Learning and Speech, Leibniz Institute for Neurobiology, Magdeburg, Germany [2] German Center for Neurodegenerative Diseases (DZNE), Partner site Magdeburg, Magdeburg, Germany [3] Center for Behavioral Brain Sciences, Magdeburg, Germany.
authors.forename: Henning
authors.initials: H
authors.lastname: Scheich
authors.affiliation: 1] Department of Experimental Neurology, Center for Stroke Research Berlin (CSB), Charité-University Medicine Berlin, Berlin, Germany [2] German Centre for Neurodegenerative Diseases (DZNE), Partner site Berlin, Berlin, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Dirnagl
authors.affiliation: 1] Project Group Neuropharmacology, Leibniz Institute for Neurobiology, Magdeburg, Germany [2] Research Institute for Applied Neurosciences (FAN) GmbH, Magdeburg, Germany.
authors.forename: Ulrich H
authors.initials: UH
authors.lastname: Schröder
authors.affiliation: Department of Experimental Neurology, Center for Stroke Research Berlin (CSB), Charité-University Medicine Berlin, Berlin, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Wunder
authors.affiliation: 1] Department of Auditory Learning and Speech, Leibniz Institute for Neurobiology, Magdeburg, Germany [2] Clinic for Neurology, Otto-von-Guericke University, Magdeburg, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Goldschmidt
mesh_terms: D000208:Acute Disease; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D001931:Brain Mapping; D002614:Chelating Agents / Q000008:administration & dosage; D004195:Disease Models, Animal; D004050:Ditiocarb / Q000008:administration & dosage; D006651:Histocytochemistry / Q000379:methods; D002546:Ischemic Attack, Transient / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D011188:Potassium / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013793:Thallium; D013794:Thallium Radioisotopes / Q000008:administration & dosage; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods
chemical_list: D002614:Chelating Agents; D013794:Thallium Radioisotopes; D004050:Ditiocarb; D013793:Thallium; D011188:Potassium