Olfaction can be impaired due to damage caused by trauma, infection, inflammation or aging. Damage can occur anywhere along the pathway from the peripheral olfactory epithelium in the nose to the cortex. The olfactory system exhibits a degree of plasticity that underlies an ability to recover function following certain types of injury. Nonetheless, lasting anosmia or hyposmia remain challenging clinical problems. At the periphery, recovery involves the generation of new olfactory neurons and related cell populations from tissue-resident stem cells. Functional recovery necessarily involves an ability to incorporate newly generated cells into the sensory system. Objectives: here, we consider mechanisms involved in damage and repair in the periphery, the olfactory epithelium in the nose. Methods: rodent models have long been used to experimentally injure the olfactory epithelium, including chemical injuries (including Triton X-100, zinc sulfate, methyl bromide, methimazole), surgical injury (olfactory bulb ablation, Cranial Nerve 1 section, blunt head trauma), genetic or pharmacogenetic alterations (gene deletion, conditional gene knockout, conditional toxin expression), or viral infection (for instance, influenza or coronavirus models). Results/conclusions: we review here details emerging from animal studies, identifying the horizontal basal cell as a reserve population, and globose basal cells as a heterogenous pool of active progenitors, harboring functional plasticity. Details regarding the functional potential and molecular mechanisms regulating basal cells are considered. Recent efforts to define patterns of olfactory epithelial damage in humans are also considered, including the potential roles of immune cells. Finally, we review potential therapeutic strategies emerging from these studies.
Funding: NIH/NIDCD