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Single-cell resolution mapping of neuronal damage in acute focal cerebral ischemia using thallium autometallography

Lookup NU author(s): Dr Iryna Ziabreva


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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 (TlDDC)-Tl-201 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.

Publication metadata

Author(s): Stober F, Baldauf K, Ziabreva I, Harhausen D, Zille M, Neubert J, Reymann KG, Scheich H, Dirnagl U, Schroder UH, Wunder A, Goldschmidt J

Publication type: Article

Publication status: Published

Journal: Journal of Cerebral Blood Flow & Metabolism

Year: 2014

Volume: 34

Issue: 1

Pages: 144-152

Print publication date: 16/10/2013

ISSN (print): 0271-678X

ISSN (electronic): 1559-7016

Publisher: Nature Publishing Group


DOI: 10.1038/jcbfm.2013.177


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Funder referenceFunder name
TSB grant
01 EO 08 01Bundesministerium fur Bildung und Forschung (Center for Stroke Research Berlin)
202213European Union
201024European Union
Exc 257Deutsche Forschungsgemeinschaft (NeuroCure Cluster of Excellence)
Sonderforschungsbereich SFB 779Deutsche Forschungsgemeinschaft (NeuroCure Cluster of Excellence)