title: Aminoglycoside Increases Permeability of Osseous Spiral Laminae of Cochlea by Interrupting MMP-2 and MMP-9 Balance.
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.
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Institute of Otolaryngology of PLA, Chinese PLA General Hospital, Beijing, 100853, People's Republic of China.
authors.forename: Dengke
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Institute of Otolaryngology of PLA, Chinese PLA General Hospital, Beijing, 100853, People's Republic of China.
authors.forename: Jianhe
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Institute of Otolaryngology of PLA, Chinese PLA General Hospital, Beijing, 100853, People's Republic of China.
authors.forename: Lidong
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Institute of Otolaryngology of PLA, Chinese PLA General Hospital, Beijing, 100853, People's Republic of China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Guo
authors.affiliation: Department of Communicative Disorders and Sciences, Center for Hearing and Deafness, the State University of New York at Buffalo, Buffalo, New York, 14214, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Sun
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Institute of Otolaryngology of PLA, Chinese PLA General Hospital, Beijing, 100853, People's Republic of China. yangsm301@263.net.
authors.forename: Shiming
authors.initials: S
authors.lastname: Yang
mesh_terms: D000583:Amikacin / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D000617:Aminoglycosides / Q000009:adverse effects*; D000818:Animals; D005070:Evans Blue / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000187:drug effects / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000187:drug effects / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology; D010011:Osteocytes / Q000187:drug effects*; D010118:Oxytetracycline / Q000494:pharmacology; D010539:Permeability / Q000187:drug effects*; D051381:Rats; D012533:Scala Tympani / Q000378:metabolism; D013136:Spiral Ganglion / Q000187:drug effects; D013137:Spiral Lamina / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000617:Aminoglycosides; D061965:Matrix Metalloproteinase Inhibitors; D005070:Evans Blue; D000583:Amikacin; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D010118:Oxytetracycline
keywords: Amikacin; Cochlear permeability; Matrix metalloprotease; Scala tympani; Spiral ganglion neurons