288 DEVELOPMENT OF AN EXPERIMENTAL MODEL FOR ANOSMIA FOR CELL THERAPY PURPOSES

Abstract

The olfactory sense is most important for social and environmental interaction, contributing to the quality of life. Its dysfunction, called anosmia, is followed by severe social problems. Anatomically, this is associated with changes in the nasal epithelium and the central and peripheral nervous system. Anosmia can be caused by infection, trauma, and cancer. Along with other olfactory disorders, anosmia occurs in ~50% of the population between 65 and 80 years of age and 75% of the population above 80 years of age. Because of the dramatic effect of such diseases, we aim to develop an experimental model of anosmia in rats as well as to culture stem cells that may be used for future cell therapy purposes. We used 15 adult Wistar rats (60 days). As a first step of our project, the animals were submitted to an experimental surgery to ablate the olfactory bulb (OB). The ocular bulb was used as reference to localizate transfrontal craniotomy. The surgical time for this procedure ranged from 40 to 50 min. The olfactory bulb has an elliptical shape and consists of soft tissue, almost gelatinous, which breaks up easily when manipulated or restrained by surgical instruments. Therefore, we chose to aspirate the tissue, using a urethral probe coupled to an aspirator. Removal of the OB resulted in bilateral cavities, elongated, situated between the cribriform plate of the ethmoid bone and brain. The postoperative period passed without major incidents. The skin suture was removed between 7 and 10 days after surgery. The animals were clinically evaluated each day for a period of 60 days. No animal showed signs of pain or discomfort, apathy, loss of appetite, or hypersensitivity in the surgical wound. However, the consumption of food and water was increased. Some animals lost their feeding selectivity, eating pieces of paper, shavings, and surgical drapes used to line the cages. In addition, we observed behavioural changes such as excitability and aggressiveness. Tests of revulsion at the smell of cats and perception of pungent odor demonstrated the lack of odor perception, consequently regarded as signs of anosmia. We conclude that the surgical technique used was effective and easy to perform in order to establish an experimental model for anosmia in rats. As a next step, potential stem cells derived from the olfactory epithelium were successfully isolated. A characterisation of these cells is currently under way, as well as preclinical tests to reveal the recovery of olfactory functions after cell therapy.