Roehm Pamela, Hoffer Michael, Balaban Carey D
Department of Otolaryngology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
Hear Res. 2007 Aug;230(1-2):43-52. doi: 10.1016/j.heares.2007.04.005. Epub 2007 Jun 2.
Studies of transtympanic gentamicin have focused on clinical use and outcomes. This study presents evidence of bilateral uptake and retention of gentamicin in certain inner ear cells and structures following transtympanic gentamicin application. Middle ear application of gentamicin was performed by either minipump (Alza model, 2002) or transtympanic injection in a chinchilla model. Histological sections of decalcified temporal bones were stained to identify the distribution of gentamicin. Using both anti-gentamicin immunohistochemistry and autoradiography of tracer amounts of tritiated gentamicin, Scarpa's and spiral ganglion cells, stria vascularis, and vestibular dark cells of the injected ear were found to have higher levels of gentamicin and retain it within cell bodies while staining levels fell to background levels in the rest of the injected ear over the course of 14 days. There was no evidence of an apical to basal gradient of anti-gentamicin staining within the spiral ganglion. Contralateral inner ear cells showed light anti-gentamicin staining. Cell bodies in the ipsilateral dorsal cochlear nucleus bordering the cochlear aqueduct (CA) showed a lateral to medial gradient of gentamicin staining, suggesting the CA as a potential site of transfer of gentamicin to the contralateral ear. Direct effects of aminoglycosides on ganglion cells may have implications on both the success of cochlear implantation in patients deafened following systemic aminoglycoside therapy and on the advisability of clinical practices of transtympanic gentamicin therapy and ototopic aminoglycoside treatment.
经鼓膜庆大霉素的研究主要集中在临床应用和疗效方面。本研究提供了证据,表明经鼓膜应用庆大霉素后,庆大霉素在某些内耳细胞和结构中存在双侧摄取和潴留现象。在栗鼠模型中,通过微型泵(Alza型号,2002)或经鼓膜注射进行中耳庆大霉素给药。对脱钙颞骨的组织学切片进行染色,以确定庆大霉素的分布。使用抗庆大霉素免疫组织化学和微量氚标记庆大霉素的放射自显影技术,发现注射耳的斯卡帕神经节和螺旋神经节细胞、血管纹以及前庭暗细胞中庆大霉素水平较高,并在细胞体内潴留,而在注射耳的其余部分,染色水平在14天内降至背景水平。在螺旋神经节内没有证据表明抗庆大霉素染色存在从顶端到基部的梯度。对侧内耳细胞显示轻度抗庆大霉素染色。与蜗水管(CA)相邻的同侧背侧蜗神经核中的细胞体显示庆大霉素染色从外侧到内侧的梯度,提示蜗水管可能是庆大霉素向对侧耳转移的潜在部位。氨基糖苷类药物对神经节细胞的直接作用可能对全身应用氨基糖苷类药物致聋患者的人工耳蜗植入成功率以及经鼓膜庆大霉素治疗和耳局部氨基糖苷类药物治疗的临床实践可行性都有影响。