TY  - JOUR
AU  - Rueger, M.A.
AU  - Backes, H.
AU  - Walberer, M.
AU  - Nleumaier, B.
AU  - Ullrich, R.
AU  - Simar, M.L.
AU  - EMig, B.
AU  - Fink, G. R.
AU  - Hoehn, M.
AU  - Graf, R.
AU  - Schroeter, M.
TI  - Noninvasive imaging of endogenus neural stem cell mobilization in vivo using positron emission tomography
JO  - The journal of neuroscience
VL  - 30
SN  - 0270-6474
CY  - Washington, DC
PB  - Soc.
M1  - PreJuSER-9719
SP  - 6454 - 6460
PY  - 2010
N1  - This work was supported by the Koeln Fortune Program/Faculty of Medicine, University of Cologne, Germany (144/2007).
AB  - 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'-[(18)F]fluoro-l-thymidine ([(18)F]FLT) that enables imaging and measuring of proliferation to noninvasively detect endogenous neural stem cells in the normal and diseased adult rat brain in vivo. This method indeed visualized neural stem cell niches in the living rat brain, identified as increased [(18)F]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 [(18)F]FLT-PET to visualize neural stem cell mobilization. Moreover, [(18)F]FLT-PET allowed for an in vivo quantification 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 [(18)F]FLT-PET could be used to monitor the effects of drugs aimed at expanding the neural stem cell niche.
KW  - Animals
KW  - Brain: drug effects
KW  - Brain: embryology
KW  - Brain: metabolism
KW  - Brain: physiology
KW  - Brain: radionuclide imaging
KW  - Brain Ischemia: metabolism
KW  - Brain Ischemia: physiopathology
KW  - Cell Movement: drug effects
KW  - Cell Movement: physiology
KW  - Cell Proliferation: drug effects
KW  - Cells, Cultured
KW  - Dideoxynucleosides: metabolism
KW  - Fibroblast Growth Factor 2: pharmacology
KW  - Insulin: pharmacology
KW  - Intracellular Signaling Peptides and Proteins
KW  - Lateral Ventricles: drug effects
KW  - Lateral Ventricles: physiology
KW  - Membrane Proteins: pharmacology
KW  - Neurons: metabolism
KW  - Neurons: physiology
KW  - Positron-Emission Tomography: methods
KW  - Rats
KW  - Stem Cells: metabolism
KW  - Stem Cells: physiology
KW  - Dideoxynucleosides (NLM Chemicals)
KW  - Insulin (NLM Chemicals)
KW  - Intracellular Signaling Peptides and Proteins (NLM Chemicals)
KW  - Membrane Proteins (NLM Chemicals)
KW  - delta protein (NLM Chemicals)
KW  - Fibroblast Growth Factor 2 (NLM Chemicals)
KW  - alovudine (NLM Chemicals)
KW  - J (WoSType)
LB  - PUB:(DE-HGF)16
C6  - pmid:20445071
UR  - <Go to ISI:>//WOS:000277358300031
DO  - DOI:10.1523/JNEUROSCI.6092-09.2010
UR  - https://juser.fz-juelich.de/record/9719
ER  -