脑源性神经营养因子在庆大霉素耳毒性后的保护作用。

The protective effect of brain-derived neurotrophic factor after gentamicin ototoxicity.

作者信息

Lopez I, Honrubia V, Lee S C, Chung W H, Li G, Beykirch K, Micevych P

机构信息

Victor Goodhill Ear Center, Division of Head and Neck Surgery, School of Medicine, University of California, Los Angeles 90095-1624, USA.

出版信息

Am J Otol. 1999 May;20(3):317-24.

PMID:10337971

Abstract

HYPOTHESIS

Brain-derived neurotrophic factor (BDNF) influences the process of hair cell recovery in the vestibular sensory epithelium of the chinchilla after local application of gentamicin (GM).

BACKGROUND

Hair cell regeneration in the inner ear after GM ototoxicity has been demonstrated. However, the mechanisms responsible for this recovery have yet to be completely elucidated. This report examines the protective and proliferative effects that BDNF exerts on vestibular hair cells in experiments designed to further elucidate the mechanisms of hair cell regeneration.

METHODS

The inner ears of three separate groups of chinchillas were treated with GM only, GM and BDNF simultaneously, and GM followed by BDNF 1 week later. The numbers of hair and supporting cells in the horizontal cristae of each group were then estimated at 1, 2, 4, and 8 weeks, and the data were compared.

RESULTS

Type I hair cells after GM treatment completely disappeared. After simultaneous BDNF and GM treatment, their numbers decreased to 23% at 1 week and progressively disappeared by week 8. When BDNF was applied 1 week after GM administration, type I hair cells recovered to 12% at week 4 and 28% at week 8. Type II hair cells after GM treatment decreased to 15%, but recovered to 83% 4 weeks later. Simultaneous administration of BDNF and GM prevented the ototoxic effects of GM alone. When BDNF was administered 1 week after GM, type II hair cell recovery was accelerated and was greater than after GM alone (81% versus 18%). Supporting cells after GM treatment decreased to 74% at 1 week after treatment, recovered to 91% at 2 weeks, and remained at 86% at 4 weeks and 85% at 8 weeks. With the simultaneous administration of BDNF and GM, supporting cells significantly decreased at 2 weeks after treatment (63%), but recovered to normal by week 8.

CONCLUSIONS

These results suggest that BDNF provided simultaneously with GM minimizes the ototoxic effect of GM on type II hair cells. The increase in the number of new hair cells when BDNF is provided after ototoxic damage is evidence of the proliferative capacity of this neurotrophic factor.

摘要

假设

脑源性神经营养因子（BDNF）影响在局部应用庆大霉素（GM）后绒鼠前庭感觉上皮中毛细胞的恢复过程。

背景

GM耳毒性后内耳毛细胞再生已得到证实。然而，负责这种恢复的机制尚未完全阐明。本报告在旨在进一步阐明毛细胞再生机制的实验中研究了BDNF对前庭毛细胞的保护和增殖作用。

方法

三组不同的绒鼠内耳分别仅用GM处理、同时用GM和BDNF处理以及在GM处理1周后再用BDNF处理。然后在1、2、4和8周时估计每组水平嵴中毛细胞和支持细胞的数量，并比较数据。

结果

GM处理后I型毛细胞完全消失。BDNF和GM同时处理后，其数量在1周时降至23%，并在第8周逐渐消失。当在GM给药1周后应用BDNF时，I型毛细胞在第4周恢复到12%，在第8周恢复到28%。GM处理后II型毛细胞降至15%，但4周后恢复到83%。BDNF和GM同时给药可防止GM单独的耳毒性作用。当在GM给药1周后给予BDNF时，II型毛细胞恢复加速，且大于单独GM处理后（81%对18%）。GM处理后支持细胞在处理后1周降至74%，在2周恢复到91%，在4周保持在86%，在8周保持在85%。BDNF和GM同时给药时，支持细胞在处理后2周显著减少（63%），但在第8周恢复正常。