The purpose of the Clinical Olfactory Research Center continues to be the identification and evaluation of mechanisms underlying human olfactory dysfunction, and to this purpose we now add therapeutics. There are two general categories for human olfactory dysfunction; a) problems with odorant access to the receptors which includes conductive airway problems and b) neurological problems. In regards to (a) we will develop, based on engineering principles of fluid mechanics and mass transfer, numerical 3-D finite element computer models of the human and rat nose. These will let us determine regional nasal airflows and the amount of each odorant likely deposited at each position along the mucosal as a function of such variables as odorant mucus solubility, sniff flow rate and a number of clinically relevant deviations in the nasal cavity. In a complementary study, we will use CT imaging to measure regions of the nasal cavity and using olfactory test scores, we will related nasal morphology to olfactory funciton. We will determine whether odor perception with a cold is related to mucus solubility of the odorants since, with the added congestion, relatively fewer molecules of the more soluble odorants likely reach the olfactory cleft. In regards to (b), we will show how the anatomy, physiology and behavior of recovery relate to each other following mucosal lesion. We will determine whether odor quality change with recovery; whether delayed functional reconnection of the epithelium to the bulb explains the long delay observed in the recovery of function relative to the epithelial recovery; and whether there is a relationship between the topography or extent of epithelial damage and the particular odors compromised. Likewise, at the bulbar level, we will determine whether focally restricted lesion, based upon RB-8 expression and 2-DG activation patterns, result in selective deficits in odorant identification. We will use a transgenic mouse, whose mucosa mimics the """"""""quiescent"""""""" appearance of some dysosmic patients, as a model for the histopathology of olfactory dysfunction. In another animal model we will pursue the possibility that IGF-1 is a trophic factor on which newly-born olfactory neurons depend, and, if so, we will investigate whether IGF-1 represents a therapeutic strategy for reinnervating the deafferented bulb. In another possible therapeutic strategy, we will pursue the transplanting of basal cells into lesioned epithelium to generate new neurons. Recognizing that in many patients dysosmia follows a URI, we will investigate, using the animal model, the anatomical, behavioral and physiological consequences of viral insult. We will improve the Odorant Confusion Matrix and other more direct tests of odorant dissimilarity as they reflect the mechanisms underlying olfactory disorders, and we will develop a device for intranasal optical recording and odorant delivery in humans which will record mucosal activity patterns and separate conductive problems from neural problems. We will follow the progressive deterioration of the olfactory system which attends HIV infection, and we will test whether olfactory deficits predict the onset of AIDS dementia. A self-supporting clinical serves as a resource for subjects and a focus for generating and testing ideas about the mechanisms underlying dysosmia.
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