BASE-TO-APEX GRADIENT OF CELL-PROLIFERATION IN THE CHICK COCHLEA FOLLOWING KANAMYCIN-INDUCED HAIR CELL LOSS

In order to elucidate the mechanisms that drive cell proliferation in the avian cochlea, we investigated the spatio-temporal relationship be tween hair cell degeneration and cell proliferation after aminoglycosi de ototoxicity. Neonatal chicks were given a daily intramuscular injec tion of kanamycin (KM) at 400 mg/kg per day for 10 consecutive days. A t various times during or after KM administration, proliferating cells were labeled over a period of 2 days with bromodeoxyuridine (BrdU) an d visualized with peroxidase immunohistochemistry. Changes in the loca tion of the hair cell lesion during the KM treatment were monitored by phalloidin immunofluorescence or scanning electron microscopy. Hair c ell loss began at the base of the cochlea 6 days after the start of KM injections, whereas cell proliferation was first observed in the basa l region between days 6 and 8 of the KM treatment. This indicates that the latency between cell loss and cell proliferation is less than 48 h. The region of cell proliferation shifted from the base toward the a pex of the cochlea over a period of 6-8 days, but cell proliferation i n a specific region of the cochlea only occurred for 2-4 days. The lat ency as well as the total duration of cell proliferation after KM otot oxicity was virtually equivalent to that observed after acoustic traum a (Hashino and Salvi, 1993), suggesting that similar cellular events a re involved in triggering cell proliferation after mechanical destruct ion and metabolic destruction of avian hair cells. The spatio-temporal gradient of cell proliferation followed the pattern of hair cell loss , suggesting that some aspect of hair cell degeneration provides trigg er signals for cell proliferation.