Lichtenhan J T, Hartsock J, Dornhoffer J R, Donovan K M, Salt A N
Washington University School of Medicine, Department of Otolaryngology, Saint Louis, MO 63110, USA.
Washington University School of Medicine, Department of Otolaryngology, Saint Louis, MO 63110, USA.
J Neurosci Methods. 2016 Nov 1;273:201-209. doi: 10.1016/j.jneumeth.2016.08.005. Epub 2016 Aug 6.
Administering pharmaceuticals to the scala tympani of the inner ear is a common approach to study cochlear physiology and mechanics. We present here a novel method for in vivo drug delivery in a controlled manner to sealed ears.
Injections of ototoxic solutions were applied from a pipette sealed into a fenestra in the cochlear apex, progressively driving solutions along the length of scala tympani toward the cochlear aqueduct at the base. Drugs can be delivered rapidly or slowly. In this report we focus on slow delivery in which the injection rate is automatically adjusted to account for varying cross sectional area of the scala tympani, therefore driving a solution front at uniform rate.
Objective measurements originating from finely spaced, low- to high-characteristic cochlear frequency places were sequentially affected. Comparison with existing methods(s): Controlled administration of pharmaceuticals into the cochlear apex overcomes a number of serious limitations of previously established methods such as cochlear perfusions with an injection pipette in the cochlear base: The drug concentration achieved is more precisely controlled, drug concentrations remain in scala tympani and are not rapidly washed out by cerebrospinal fluid flow, and the entire length of the cochlear spiral can be treated quickly or slowly with time.
Controlled administration of solutions into the cochlear apex can be a powerful approach to sequentially effect objective measurements originating from finely spaced cochlear regions and allows, for the first time, the spatial origin of CAPs to be objectively defined.
向内耳鼓阶给药是研究耳蜗生理和力学的常用方法。我们在此介绍一种以可控方式向封闭耳朵进行体内药物递送的新方法。
将耳毒性溶液从密封于耳蜗顶端小孔的移液管注入，使溶液沿鼓阶长度逐渐向基部的蜗水管推进。药物可以快速或缓慢递送。在本报告中，我们重点关注缓慢递送，即注射速率会自动调整以适应鼓阶变化的横截面积，从而以均匀速率推动溶液前沿。
来自精细间隔的、低到高特征性耳蜗频率位置的客观测量结果依次受到影响。与现有方法的比较：向耳蜗顶端进行药物的可控给药克服了先前方法（如在耳蜗基部用注射移液管进行耳蜗灌注）的一些严重局限性：所达到的药物浓度得到更精确的控制，药物浓度保留在鼓阶中，不会被脑脊液流动迅速冲走，并且耳蜗螺旋的整个长度可以根据时间快速或缓慢地进行处理。
向耳蜗顶端进行溶液的可控给药可以成为一种有力的方法，依次影响来自精细间隔的耳蜗区域的客观测量结果，并首次能够客观地定义复合动作电位（CAPs）的空间起源。
