RECONSTITUTION OF THE RAT OLFACTORY EPITHELIUM AFTER METHYL BROMIDE-INDUCED LESION

The olfactory epithelium and its neuronal population are known to have a substantial capacity to recover after either direct injury or damag e to the olfactory nerve. However, the mechanisms underlying that capa city for recovery, and indeed the limits on the recovery process, are not well understood The aim of this study is to describe in detail the way in which the olfactory epithelium reconstitutes after direct inju ry. Adult male rats were exposed to 330 ppm methyl bromide (MeBr) gas for a single 6-hour period. The exposure destroys all of the neurons a nd sustentacular cells in over 95% of the olfactory epithelium of food -restricted rats and in over 90% of the epithelium in ad-libitum-fed r ats of the same weight, yet substantial recovery of the olfactory epit helium occurs. In response to the lesion, cellular proliferation incre ases markedly beginning between 24 and 48 hours, peaks at 1 week, and persists at levels higher than the control level for more than 4 weeks after MeBr exposure. Even though proliferation accelerates promptly, the beginning of neuronal reconstitution is delayed; only a few immatu re neurons are observed 3 days after the lesion, yet they reappear in large numbers by the end of the first week. The first mature neurons e merge between 7 and 14 days after lesion and increase to near normal n umbers by 4-6 weeks. In association with the restoration of the neuron al population, basal cell proliferation returns to control levels betw een 4 and 6 weeks after damage. Likewise, sustentacular cells, identif iable by anticytokeratin 18 labeling, reappear rapidly and reform a di stinct lamina in the superficial aspect of the epithelium. They closel y resemble their counterparts in control epithelium with regard to dis position and shape by 3 weeks after lesion and with regard to expressi on of olfactory-specific cytochrome P450s by 8 weeks. Thus, most areas of the epithelium are restored to a near normal appearance and cellul ar composition by the end of 8 weeks, suggesting that the MeBr paradig m for lesioning the epithelium offers significant advantages over tech niques such as Triton X-100 or ZnSO4 irrigation. However, not all meas ures of epithelial status are normal even at 8 weeks. Immature neurons remain slightly more numerous than normal at this time. Furthermore, some areas of the olfactory epithelium do not recover after MeBr lesio n and are replaced by respiratory epithelium. By documenting the event s and the extent of olfactory epithelial reconstitution after direct i njury, the present results serve as a foundation for future studies de signed to identify the mechanisms under lying epithelial recovery and the difference between areas of the epithelium that reconstitute fully after lesion and those where the recovery process fails. (C) 1995 Wil ey-Liss, Inc.