Single Cell Tracking of Neural Progenitors labeled in vivo with Micron Sized Particles of Iron Oxide (MPIO) into Specific Layers of the Olfactory Bulb
نویسندگان
چکیده
Introduction Rodent neural progenitor cells (NPCs) continually populate the olfactory bulb (OB). Once in the olfactory bulb, these NPCs migrate radially and integrate into preexcising neural circuitry. Based on histological evidence, the NPC distribution within the OB as well as their number can be effected when animals are continually exposed to odors [1,2]. However, a recent report provides contradictory evidence that neither the number nor the distribution of NPCs in the olfactory bulb changes with odor [3]. Since these studies relied exclusively on histology, it remains unclear whether odor would effect the NPC distribution globally in the olfactory bulb of a live animal. To overcome this limitation, MRI was used to characterize the distribution of NPCs in the olfactory bulb of both naïve and odor stimulated animals. It has previously been demonstrated that micron particles of iron oxide (MPIOs) can be used to label endogenous neural precursors after direct injection of MPIOS and migration of NPCs detected with MRI [4, 5]. It has also been demonstrated that Manganese enhanced MRI (MEMRI) can delineate layers present in the olfactory bulb [6]. Here MPIOs were used to label the neural progenitors that originate in the subventricular zone of adult rodents. At four weeks post injection, the animals were imaged at 50μm isotropic resolution. At this resolution individual NPCs could be identified and counted within the olfactory bulb in a layer specific manner with the aid of MEMRI. Materials and Methods Seven, 6 week old Sprague-Dawley rats (Charles River Laboratories, Inc., Wilmington, MA) were stereotactically injected with 1.4x10 MPIOs (Bangs Laboratories, Inc., Fishers, IN). Four animals were exposed to amyl acetate for 4 weeks. Three animals were not exposed to amyl acetate (naïve). Prior to MRI all animals were infused w/ 37mg MnCl2/kg. MRI data was acquired on an 11.7 T animal MRI system (30 cm 11.7 T horizontal magnet, Magnex Scientific, Oxford, England, MRI Electronics, Bruker Biospin, Billerica, MA, equipped with 12 cm-id gradients, Resonance Research Inc, Billerica, MA) using a volume transmit coil and a custom built, 1 cm diameter, receive-only surface-coil. 3D Multi-gradient echo (MGE) sequences were used for MRI with the following parameters: FOV 1.28 cm x 1.44 cm x 0.96 cm, Matrix 256 x 288 x 192 (50 μm isotropic resolution), 50 kHz bandwidth, multiple TEs 4.25, 11.75, 19.25, and 26.75 ms, and TR 32 ms. Images were reconstructed using IDL. Images from the second and third echo were thresholded at 3 x standard deviation of the noise of the surrounding pixels to select the MPIOs from the background. This thresholded mask was overlaid on the original images from the first echo. From these composite images, the MPIOs were counted in each layer of the olfactory bulb.
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