MRI T2* Hypointensity at the Glia Limitans in the Olfactory Bulb is due to High Iron in the Olfactory Ensheathing Cells in Young Adult Mouse

Motivation: Brain iron overload is a hallmark of neuroinflammatory diseases. Here, T2*-weighted MRI detected an increase of hypointensity at the olfactory nerve layer (ONL) in young mice from 3 to 12 weeks. Goal(s): Find out the cellular origins of T2*-hypointensity. Approach: MRI guided immunohistochemistry and electron-microscopy study. Results: We found that the T2*-hypointensity is due to high iron in olfactory ensheathing cells (OECs). OECs form glia limitans, ensheath bundles of olfactory axons, and are the main phagocytic cells in olfactory system to aid regeneration of olfactory neurons. Near high-iron region, lipofuscin, a neuroinflammation marker was found in activated microglia as early as 6 weeks. Impact: Guided by MRI, we found that there is an extraordinarily high level of intrinsic iron in the olfactory ensheathing cells in olfactory nerve layer in young mice, which indicates their phagocytic and neuroprotection functions during rapid olfactory sensory neuron turnover.