Magnetic resonance imaging of the migration of neuronal precursors generated in the adult rodent brain

Abstract

Neural progenitor cells (NPCs) reside within the subventricular zone (SVZ) in rodents. These NPCs give rise to neural precursors in adults that migrate to the olfactory bulb (OB) along a welldefined pathway, the rostral migratory stream (RMS). Here we demonstrate that these NPCs can be labeled, in vivo, in adult rats with fluorescent, micron-sized iron oxide particles (MPIOs), and that magnetic resonance imaging (MRI) can detect migrating neural precursors carrying MPIOs along the RMS to the OB. Immunohistochemistry and electron microscopy indicated that particles were inside GFAP + neural progenitor cells in the SVZ, migrating PSA-NCAM + and Doublecortin + neural precursors within the RMS and OB, and Neu-N + mature neurons in the OB. This work demonstrates that in vivo cell labeling of progenitor cells for MRI is possible and enables the serial, non-invasive visualization of endogenous progenitor/precursor cell migration.

Tracking Induced Pluripotent Stem Cells–Derived Neural Stem Cells in the Central Nervous System of Rats and Monkeys

“…Brain tissues were fixed in 4% PFA overnight, dehyrated in 30% sucrose solution, frozen on dry ice, and cryosected as 30-lm slices for histology according to the MRI images. The sections were doubly stained by Hematoxylin & Eosin (H&E) and PB to detect intracellular iron oxide particles (Shapiro et al, 2006).…”

Maturation of the Olfactory Bulbs: MR Imaging Findings

“…Cytoarchitectural studies have shown that in rodents, peripheral neurons are, to some extent, derived from migratory neurons originating from the prestriatal subventricular zone but can also originate from progenitor cells organized around the core of the OBs. 15,16 A similar migratory pathway has only been identified once in humans, 17 but this finding is controversial. 18 These peripheral cells will eventually serve as a relay to the olfactory neurons from the nasal cavity.…”

In vivoimaging of endogenous neural stem cells in the adult brain

“…Labels can be micro-injected directly into (or close to) the neurogenic niches, or they can be coupled to a vector in order to specifically target certain cells. Direct injection of a paramagnetic label such as small particles of iron oxide allows for cell detection using magnetic resonance imaging (MRI) with excellent spatial resolution on the single cell level (Figure 1) [54][55][56][57][58][59] . However, this type of labeling is neither specific for a certain cell type, nor does it reflect cell viability, as only the particles themselves are visualized [53] .…”

“…However, this type of labeling is neither specific for a certain cell type, nor does it reflect cell viability, as only the particles themselves are visualized [53] . Moreover, directly injecting iron oxide in e.g., the lateral ventricles of the brain results in image distortion in the region of injection, allowing only for the detection of cells migrating away from the injection site [54,57,58] . A more specific in vivo labeling approach is achieved by attaching an imaging label to a retroor lentiviral vector, thus targeting proliferating cells in particular.…”