利用小鼠模型对耳蜗后听觉通路进行特异性靶向，以实现最佳药物输送。

Specific targeting of retrocochlear auditory pathway for optimal pharmacotherapy delivery using a mouse model.

机构信息

Johns Hopkins School of Medicine, Baltimore, Maryland, USA.

出版信息

Otol Neurotol. 2012 Aug;33(6):1085-91. doi: 10.1097/MAO.0b013e31825e7e12.

DOI:10.1097/MAO.0b013e31825e7e12

PMID:22772010

Abstract

HYPOTHESIS

Optimal pharmacotherapy entails a safe delivery method that specifically targets auditory structure(s) of interest. A retrocochlear neuronal tracer may enable comparison of various pharmacotherapy delivery methods and localization of the drug along the auditory pathway.

BACKGROUND

Sensorineural hearing loss (SNHL) can involve cochlear hair cell or neural cell death, which often is accompanied by secondary degeneration of central auditory neurons. Targeting the precise location of nerve degeneration is important for treatment success. To be clinically relevant, the method of drug delivery must be safe and reliable while being maximally absorbed by the relevant inner ear structures of interest.

METHODS

We compared 3 methods of FluoroGold (FG) delivery, a retrograde neuronal tracer, in delineating the retrocochlear auditory pathway using a normal-hearing strain of CBA mice. FG was delivered either intratympanic (IT), intracochlear (IC), or through the round window (RW). Five days after FG injection, mice were sacrificed for cell counts in the cochlear nucleus (CN), superior olivary complex (SOC), and the lateral lemniscus (LL).

RESULTS

Although neurons in the CN and SOC were abundantly labeled by FG in all 3 injection methods, the IT method was the most reproducible and specific. The average cells for the CN, SOC, and LL were 851 ± 121, 2629 ± 367, and 112 ± 30, respectively. Accurate cell counts could not be established for the IC and RW injection methods because of nonspecific cell staining. Only 1 of the 5 IC-injected mice had specific labeling along the retrocochlear auditory pathway. Cell counts for the single mouse with specific IC staining in the CN, SOC, and LL were 177, 1839, and 56, respectively. Similarly, 2 of the 5 RW-injected mice had specific labeling, whereas the rest were nonspecific. The average cell counts for the 2 mice with specific labeling in the CN, SOC, and LL was 723.5 ± 580.0, 2173.5 ± 998.0, and 131.5 ± 8.0, respectively.

CONCLUSION

The IT injection method resulted in reproducible, specific staining of neuronal cells along the retrocochlear auditory pathway compared with the RW or IC route of delivery.

摘要

假设

最佳药物治疗需要一种安全的给药方法，该方法专门针对听觉结构。逆行神经元示踪剂可用于比较各种药物治疗的给药方法，并确定药物在听觉通路上的位置。

背景

感音神经性听力损失（SNHL）可涉及耳蜗毛细胞或神经元死亡，通常伴有中枢听觉神经元的继发性变性。针对神经变性的确切位置对于治疗成功很重要。为了具有临床相关性，药物递送方法必须安全可靠，同时最大限度地被相关的内耳结构吸收。

方法

我们比较了三种氟金胺（FG）给药方法，一种逆行神经元示踪剂，在使用 CBA 正常听力品系小鼠描绘耳蜗后听觉通路。FG 通过鼓室内（IT）、耳蜗内（IC）或圆窗（RW）给药。FG 注射后 5 天，处死小鼠，计算耳蜗核（CN）、上橄榄复合体（SOC）和外侧丘系（LL）中的细胞数。

结果

尽管 CN 和 SOC 中的神经元均通过三种注射方法被 FG 大量标记，但 IT 方法最具可重复性和特异性。CN、SOC 和 LL 的平均细胞数分别为 851±121、2629±367 和 112±30。由于非特异性细胞染色，无法为 IC 和 RW 注射方法建立准确的细胞计数。只有 5 只 IC 注射小鼠中的 1 只具有沿耳蜗后听觉通路的特异性标记。具有特异性 IC 染色的单只小鼠的 CN、SOC 和 LL 的细胞计数分别为 177、1839 和 56。同样，5 只 RW 注射小鼠中有 2 只具有特异性标记，其余为非特异性。2 只具有特异性标记的小鼠的 CN、SOC 和 LL 的平均细胞计数分别为 723.5±580.0、2173.5±998.0 和 131.5±8.0。