Magnetic resonance imaging of migrating neuronal precursors in normal and hypoxic-ischemic neonatal rat brains by intraventricular MPIO labeling

In this study, 10-day-old normal rats (n=6) and hypoxic-ischemic (H-I) neonatal rats (n=6) were injected with the micronsized iron oxide particles (MPIOs) into the anterior lateral ventricle. 2D and 3D high-spatial resolution MRI were performed with a 7T animal scanner 1 day before the MPIOs injection and hour 3, day 3, day 7 and day 14 after the MPIOs injection. Intraperitoneal injections of 5-bromo-2′-deoxyuridine (BrdU) were used to label newly produced cells, and were given thrice daily for 2 days before sacrifice. Immunohistochemistry and Prussian blue staining indicated that iron particles were inside the nestin+ and BrdU+ neural progenitor cells (NPCs), glial-fibrillary-acidic-protein-positive (GFAP+) astrocytes-like progenitor cells, and neuronal-nuclei-positive (NeuN+) mature neurons. Here we demonstrate that, in normal neonatal rat brain, the migrating pathway of the endogenous NPCs with MPIO is mainly along the rostral migratory stream to the olfactory bulb. In H-I neonatal rat brain, the migration of endogenous NPCs with MPIO is mainly towards the ischemic regions. Therefore, in vivo magnetic cell labeling of endogenous NPCs with MPIO and subsequently non-invasive, serial MRI monitoring should open up a new approach to probe into the mechanism of cell migration in the developmental brain under physiological and pathologic conditions.