QUANTIFICATION OF THE PROCESS OF HAIR CELL LOSS AND RECOVERY IN THE CHINCHILLA CRISTA-AMPULLARIS AFTER GENTAMICIN TREATMENT

The degree of ototoxic drug sensitivity and hair cell repair was deter mined in the chinchilla horizontal crista ampullaris after intraotic a dministration of gentamicin. Histological evaluation was made of 22 cr istae ampullaris from one normal and six post-treatment (PT) animal gr oups killed at 1, 4, 7, 14, 25, and 56 days. New hair cell production was quantified, using the dissector technique. Transmission electron m icroscopy was used to investigate the ultrastructural characteristics of the hair cells in the regenerated epithelium At 1 day PT, type I an d II hair cells presented cytoplasmic vacuolization, swollen nerve cal yces and 20% of type I and 18% of type II hair cells were lost. At 4 d ays PT, 95% of type I hair cells and 14% of type II hair cells had dis appeared. In addition, most of the type II hair cells showed clumping of nuclear material. Nerve fibers were not found in the sensory epithe lium, but were still observed below the basal lamina. Supporting cells appeared unaffected, maintaining their location in the crista. At 1 a nd 4 days PT, the damage to hair cells was more pronounced in the cent ral region of the crista ampullaris. The degree of ototoxic damage at 7 days was similar to that of 14 days: no type I hair cells were prese nt and most of the type II hair cells had disappeared: supporting cell nuclei began to occupy the apical part of the sensory epithelium and most of the nerve fibers had retracted. Quantitatively, 87 and 93% of type II hair cells were lost at 7 and 14 days PT, respectively. Initia l signs of hair cell recovery began at 28 days PT; immature type II-li ke hair cells appeared, supporting cell nuclei began to align at the b ase of the sensory epithelium and nerve fibers penetrating the basal l amina were observed. No type I hair cells were found, but 40% of the n ormal number of type II hair cells were present. Hair cells appeared t o regenerate in the peripheral areas of the cristae ampullaris first. At 56 days PT, an increase in the number of mature type II hair cells was present, supporting cells were aligned at the base of the epitheli um, and more nerve fibers appeared to penetrate the basal lamina to th e sensory epithelium. Although type I hair cells were absent from the epithelium, 55% of the normal number of type II hair cells were presen t. At this time, more regenerated hair cells were located in the cente r of the cristae ampullaris as compared to the periphery. At the trans mission electron microscopic level, type II hair cells at different st ages of maturation were observed. Some exhibited mature stereocilia. a cuticular plate, and terminal endings with synaptic specialization op posing these hair cells. In conclusion, type I hair cells were more se nsitive than type II hair cells to gentamicin intoxication (as they di sappeared as early as 4 days PT). After 56 days PT, the number of type II hair cells reached 55% of normal. No type I hair cells had regener ated at this time. These results demonstrate quantitatively the differ ential ototoxic sensitivity and regenerative capacity of hair cells. ( C) 1997 ISDN.