1. Non-invasive imaging of endogenous neural stem cell mobilization in vivo using Positron Emission Tomography
- Author
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Heiko Backes, Roland T. Ullrich, Michael Schroeter, Beata Emig, Marie-Lune Simard, Bernd Neumaier, Rudolf Graf, Mathias Hoehn, Gereon R. Fink, Maria Adele Rueger, and Maureen Walberer
- Subjects
Pathology ,pharmacology [Fibroblast Growth Factor 2] ,metabolism [Stem Cells] ,Hippocampus ,Endogeny ,Brain Ischemia ,ddc:590 ,Cell Movement ,Lateral Ventricles ,physiology [Stem Cells] ,Insulin ,alovudine ,drug effects [Cell Movement] ,Cells, Cultured ,pharmacology [Insulin] ,Neurons ,pharmacology [Membrane Proteins] ,medicine.diagnostic_test ,drug effects [Lateral Ventricles] ,Chemistry ,Stem Cells ,General Neuroscience ,methods [Positron-Emission Tomography] ,Intracellular Signaling Peptides and Proteins ,Brain ,Articles ,physiology [Neurons] ,physiopathology [Brain Ischemia] ,Neural stem cell ,medicine.anatomical_structure ,metabolism [Neurons] ,Positron emission tomography ,metabolism [Dideoxynucleosides] ,drug effects [Brain] ,Fibroblast Growth Factor 2 ,physiology [Cell Movement] ,Noninvasive imaging ,medicine.medical_specialty ,metabolism [Brain Ischemia] ,Ischemia ,Subventricular zone ,Biology ,physiology [Brain] ,embryology [Brain] ,In vivo ,Physiology (medical) ,medicine ,Animals ,delta protein ,Cell Proliferation ,drug effects [Cell Proliferation] ,physiology [Lateral Ventricles] ,Dentate gyrus ,Membrane Proteins ,medicine.disease ,Dideoxynucleosides ,Rats ,metabolism [Brain] ,Positron-Emission Tomography ,radionuclide imaging [Brain] ,Neurology (clinical) ,Neuroscience - Abstract
Neural stem cells reside in two major niches in the adult brain [i.e., the subventricular zone (SVZ) and the dentate gyrus of the hippocampus]. Insults to the brain such as cerebral ischemia result in a physiological mobilization of endogenous neural stem cells. Since recent studies showed that pharmacological stimulation can be used to expand the endogenous neural stem cell niche, hope has been raised to enhance the brain's own regenerative capacity. For the evaluation of such novel therapeutic approaches, longitudinal and intraindividual monitoring of the endogenous neural stem cell niche would be required. However, to date no conclusive imaging technique has been established. We used positron emission tomography (PET) and the radiotracer 3′-deoxy-3′-[18F]fluoro-l-thymidine ([18F]FLT) that enables imaging and measuring of proliferation to noninvasively detect endogenous neural stem cells in the normal and diseased adult rat brainin vivo. This method indeed visualized neural stem cell niches in the living rat brain, identified as increased [18F]FLT-binding in the SVZ and the hippocampus. Focal cerebral ischemia and subsequent damage of the blood–brain barrier did not interfere with the capability of [18F]FLT-PET to visualize neural stem cell mobilization. Moreover, [18F]FLT-PET allowed for anin vivoquantification of increased neural stem cell mobilization caused by pharmacological stimulation or by focal cerebral ischemia. The data suggest that noninvasive longitudinal monitoring and quantification of endogenous neural stem cell activation in the brain is feasible and that [18F]FLT-PET could be used to monitor the effects of drugs aimed at expanding the neural stem cell niche.
- Published
- 2012