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

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.