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Single-cell resolution mapping of neuronal damage in acute focal cerebral ischemia using thallium autometallography
Franziska Stöber1, Kathrin Baldauf2, Iryna Ziabreva3
11] 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.
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.
Insights
Assessing acute neuronal damage from cerebral ischemia is challenging. Thallium autometallography (TlAMG) effectively maps neuronal damage with single-cell resolution in rodent models, aiding in predicting tissue viability.
Area of Science:
- Neuroscience
- Medical Imaging
- Histochemistry
Background:
- Assessing neuronal damage in acute cerebral ischemia is difficult with current imaging and microscopy.
- Middle cerebral artery occlusion (MCAO) models are used to study ischemic stroke.
- K(+) (potassium) metabolism is crucial in neuronal function and survival.
Purpose of the Study:
- To evaluate thallium autometallography (TlAMG) for mapping acute neuronal damage in focal cerebral ischemia.
- To assess the utility of TlAMG in rodent models of MCAO.
- To determine if TlAMG can predict tissue viability in hyperacute stroke.
Main Methods:
- Rodent models of MCAO were used.
- Thallium diethyldithiocarbamate (TlDDC) was intravenously injected to deliver Tl(+) to the brain.
- TlAMG was employed to detect Tl(+) uptake in neurons and astrocytes.
- Results were compared with established markers of neuronal damage.
Main Results:
- TlAMG successfully mapped neuronal damage with single-cell resolution in MCAO models.
- Reduced Tl(+) uptake was observed in ischemic territories from 15 minutes to 24 hours post-MCAO.
- Areas of reduced uptake corresponded to established neuronal damage markers at 24 hours.
- Putative penumbral zones with diminished Tl(+) uptake were identified around larger lesions.
Conclusions:
- TlAMG is a viable method for mapping acute neuronal damage in focal cerebral ischemia.
- The technique allows for single-cell resolution mapping of K(+) metabolism alterations.
- (201)TlDDC shows promise for preclinical and clinical SPECT imaging in stroke assessment and tissue viability prediction.
