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 between hair cell degeneration and cell proliferation after aminoglycoside ototoxicity. Neonatal chicks were given a daily intramuscular injection of kanamycin (KM) at 400 mg/kg per day for 10 consecutive days. At various times during or after KM administration, proliferating cells were labeled over a period of 2 days with bromodeoxyuridine (BrdU) and visualized with peroxidase immunohistochemistry. Changes in the location of the hair cell lesion during the KM treatment were monitored by phalloidin immunofluorescence or scanning electron microscopy. Hair cell loss began at the base of the cochlea 6 days after the start of KM injections, whereas cell proliferation was first observed in the basal 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 apex of the cochlea over a period of 6-8 days, but cell proliferation in a specific region of the cochlea only occurred for 2-4 days. The latency as well as the total duration of cell proliferation after KM ototoxicity was virtually equivalent to that observed after acoustic trauma (Hashino and Salvi, 1993), suggesting that similar cellular events are involved in triggering cell proliferation after mechanical destruction 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 trigger signals for cell proliferation.
Hashino
E
E
Center for Hearing and Deafness, State University of New York at Buffalo 14214, USA.
TinHan
E K
EK
Salvi
R J
RJ
D000199:Actins / Q000737:chemistry; D000818:Animals; D000831:Animals, Newborn; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000633:toxicity*; D001489:Basilar Membrane / Q000166:cytology / Q000187:drug effects* / Q000648:ultrastructure; D001973:Bromodeoxyuridine / Q000737:chemistry; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002645:Chickens; D003051:Cochlea / Q000166:cytology / Q000187:drug effects*; D006198:Hair Cells, Auditory / Q000166:cytology / Q000187:drug effects* / Q000648:ultrastructure; D007124:Immunoenzyme Techniques; D007150:Immunohistochemistry; D007273:Injections, Intramuscular; D007612:Kanamycin / Q000008:administration & dosage / Q000633:toxicity*; D008855:Microscopy, Electron, Scanning; D010590:Phalloidine / Q000737:chemistry; D013194:Staining and Labeling
D000199:Actins; D000900:Anti-Bacterial Agents; D010590:Phalloidine; D007612:Kanamycin; D001973:Bromodeoxyuridine