Damage to the olfactory periphery destroys the population of olfactory sensory neurons and, in the case of direct epithelial lesion, also eliminates other types of cells that comprise the epithelium. In marked contrast to other parts of the nervous system, there is substantial anatomical and functional recovery of the epithelium and its projection into the CNS even in the face of severe initial lesions in both humans and animals. For example, following the epithelial lesions caused by exposure of rodents to the olfactotoxin methyl bromide, the OE generally recovers to a status that is indistinguishable from normal, at least when stem and progenitor cells among the population of globose basal cells (GBCs) are spared by the lesion. In contrast to the neuropotency of GBCs in unlesioned OE some among the spared globose basal cells (GBCs) function as broadly multipotent progenitors capable of giving rise to neurons and all of the cell types of the epithelium, and stem cells are activated. The differentiative capacity of the GBCs relates in some manner to the expression of members of the basic helix-loop-helix transcription factors and is regulated in part by transcription factors of the Sox and Pax family. Remarkably, despite partial damage to the GBC population in this lesion model, the spatial patterning of odorant receptor expression is restored, suggesting that extra-epithelial cues, perhaps emanating from deeper in the mucosa, might direct aspects of that patterning. However, severe epithelial lesions--ones that destroy the vast majority of neurons--are not without consequence. For example, irreparable damage to the human OE is the proximate cause of hyposmia, dysosmia or anosmia in that substantial patient population who present with disordered smell function. In experimental animals, reinnervation of the olfactory bulb, although robust, does not fully restore the normally precise receptotopic organization of the projection. The newly generated axons target roughly the right part of the bulb, but often innervate multiple glomeruli in that locus as opposed to the usual one or two. Despite the degradation in the mapping function responsible for converting odorant stimuli into spatial patterns of neural activity, substantial function is restored after recovery from lesion. Nonetheless, recovery of the epithelium is still remarkably good by comparison with other parts of the nervous system, and may yet provide us with a better understanding of how repair might be fostered in the CNS. In addition, it remains an open question whether the tissue stem cells responsible for reconstituting the OE might function in the repair of the damaged CNS or other tissues.
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