Noninvasive Imaging of Endogenous Neural Stem Cell MobilizationIn VivoUsing Positron Emission Tomography

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 3Ј-deoxy-3Ј-[

In vivoimaging of endogenous neural stem cells in the adult brain

“…[ 18 F]FLT-PET detects ceasing glioma cell proliferation as soon as 3 d after initiation of an anti-proliferative treatment, as we have previously shown in mice and humans [69,72] . Besides tumor cells, proliferating NSCs incorporate [ 18 F]FLT both in vitro as well as in vivo after its systemic (intravenous) injection into adult rats [75] . Thus, [ 18 F]FLT labels proliferating eNSCs in the neurogenic niches of the healthy rodent brain with high sensitivity (Figure 2A), corresponding to BrdU-accumulation ( Figure 2B).…”

“…The resulting PET-signal can be quantified to reflect the extent of eNSC mobilization [75] . Using a high-resolution PET-scanner and optimizing image reconstruction, the detection level can be as low as -10 4 cells.…”

“…These processes -often referred to as neuroinflammationinvolve the rapid activation of glial cells (microglia, astrocytes) as well as recruitment of hematogenous cells (granulocytes, T-cells, monocytes/macrophages) from the blood stream [77][78][79][80][81][82] . While neuroinflammation on the one hand contributes to the evolution of secondary damage to the surrounding [75] , with permission.…”

PET imaging of neurogenic activity in the adult brain: Toward in vivo imaging of human neurogenesis

“…21 However, quantitative alterations in neurogenic activity have been difficult to measure, owing to lower differences in PET signals between the neurogenic regions and other regions of the adult brain. Recently, we succeeded in establishing quantitative PET imaging methods for evaluating neurogenic activity in the adult brain with probenecid, a drug transporter inhibitor at the blood-brain barrier (BBB).…”

“…5,12,[26][27][28] However, it has been reported that the relative rate of proliferative activity in the DG of hippocampus is similar between rodents and primates, including cynomolgus and rhesus monkeys when compared at the same age. 29 Since [ 18 F]FLT can detect cell proliferation in neurogenic regions of adult rats under physiologic conditions, 21,22 our [ 18 F]FLT-PET imaging technique with probenecid may be used to establish in vivo imaging for proliferative activity in the DG of adult monkeys. Indeed, we are attempting to establish PET imaging methods for neurogenic activity in adult rhesus monkeys.…”