Hashino E, TinHan E K, Salvi R J
Center for Hearing and Deafness, State University of New York at Buffalo 14214, USA.
Hear Res. 1995 Aug;88(1-2):156-68. doi: 10.1016/0378-5955(95)00109-h.
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.
为了阐明驱动鸟类耳蜗细胞增殖的机制，我们研究了氨基糖苷类耳毒性后毛细胞变性与细胞增殖之间的时空关系。新生雏鸡每天肌肉注射卡那霉素（KM），剂量为400mg/kg，连续注射10天。在KM给药期间或之后的不同时间，用溴脱氧尿苷（BrdU）标记增殖细胞2天，并用过氧化物酶免疫组织化学进行观察。通过鬼笔环肽免疫荧光或扫描电子显微镜监测KM治疗期间毛细胞损伤位置的变化。KM注射开始6天后，毛细胞损失从耳蜗底部开始，而细胞增殖最早在KM治疗的第6至8天在底部区域观察到。这表明细胞损失与细胞增殖之间的潜伏期小于48小时。细胞增殖区域在6 - 8天内从耳蜗底部向顶部转移，但耳蜗特定区域的细胞增殖仅持续2 - 4天。KM耳毒性后细胞增殖的潜伏期和总持续时间与声学创伤后观察到的几乎相同（Hashino和Salvi，1993），这表明在鸟类毛细胞受到机械破坏和代谢破坏后，类似的细胞事件参与触发细胞增殖。细胞增殖的时空梯度遵循毛细胞损失的模式，这表明毛细胞变性的某些方面为细胞增殖提供了触发信号。
