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Aminoglycoside Increases Permeability of Osseous Spiral Laminae of Cochlea by Interrupting MMP-2 and MMP-9 Balance

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Abstract

The spiral ganglion neurons (SGNs) located in the Rosenthal’s canal of cochlea are essential target for cochlear implant. Previous studies found that the canaliculi perforantes, small pores on the surface of the osseous spiral lamina (OSL) of the scala tympanic (ST) of cochlea, may provide communication between the cochlear perilymph and SGNs. In this study, we found that chronic treatment of aminoglycosides antibiotics, which is well known to cause sensory cell damage in the cochlea, induced significant damage of bone lining cells on the OSLs and increased the permeability of the Rosenthal’s canal. The pores among the bone lining cells became significantly wider after chronic treatment of amikacin (100 mg/kg/day for 3–7 days). Injection of Evans Blue in the ST resulted in significant increase in its migration in the modulus in the amikacin-treated cochlea compared to the control ears, suggesting increased permeability of these passages. Treatment of amikacin with oxytetracycline, an inhibitor of matrix metalloproteases (MMPs), significantly reduced the amount of dye migrated from the ST to the modiolus. These results suggest that amikacin enhanced the permeability between the ST and SGNs by increasing MMPs. Aggregating the permeability of the bone lining cells on the OSLs may benefit gene and stem cell delivery to the SGNs in the cochlea.

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Abbreviations

MMPs:

Matrix metalloproteinases

OSLs:

Osseous spiral laminaes

SGNs:

Spiral ganglion neurons

SNHL:

Sensorineural hearing loss

ST:

Scala tympani

SV:

Scala vestibule

Ami-7D:

Amikacin - 7 days

Ami-3D:

Amikacin - 3 days

Ami + Oxy-7D:

Amikacin + Oxytetracycline - 7 days

Ami + Oxy-3D:

Amikacin + Oxytetracycline - 3 days

BM:

Basement membrane

PBS:

Phosphate-buffered saline

BCA:

Bicinchonininc acid

SDS-PAGE:

Sodium dodecylsulphate-polyacrylamide gel electrophoresis

HRP:

Horseradish peroxidase

OCT:

Optimal cutting temperature (compound)

SD:

Standard deviation

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Acknowledgments

We thank Drs. Ning Yu, Nan Wu, and Ke Liu for the technical support and valuable advice. This work was supported by grants from the National Basic Research Program of China (973 Program) (nos. 2012CB967900 and 2011CBA01000), the National Natural Science Foundation of China (NSFC no. 81271082), the National High Technology Research and Development Program (863 Program) (2014AA020510). We also want to express our appreciations to Professor Jianhe Sun who passed away several months after this experiment.

Authors’ Contributions

Yang SM, Li DK, and Sun JH designed the experiment; Li DK and Sun JH performed the experiment; Li DK and Sun W wrote the paper; Guo WW and Zhao LD contributed new reagents; and Li DK, Sun W, and Yang SM analyzed data.

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Authors and Affiliations

  1. Department of Otolaryngology, Head and Neck Surgery, Institute of Otolaryngology of PLA, Chinese PLA General Hospital, Beijing, 100853, People’s Republic of China

    Dengke Li, Jianhe Sun, Lidong Zhao, Weiwei Guo & Shiming Yang

  2. Department of Communicative Disorders and Sciences, Center for Hearing and Deafness, the State University of New York at Buffalo, Buffalo, New York, 14214, USA

    Wei Sun

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  1. Dengke Li
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  2. Jianhe Sun
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  3. Lidong Zhao
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  4. Weiwei Guo
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  5. Wei Sun
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  6. Shiming Yang
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Correspondence to Shiming Yang.

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Li, D., Sun, J., Zhao, L. et al. Aminoglycoside Increases Permeability of Osseous Spiral Laminae of Cochlea by Interrupting MMP-2 and MMP-9 Balance. Neurotox Res 31, 348–357 (2017). https://doi.org/10.1007/s12640-016-9689-2

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