Effects of Combined Gentamicin and Furosemide Treatment on Cochlear Macrophages
Combining aminoglycosides and loop diuretics often serves as an effective ototoxic approach to deafen experimental animals. The treatment results in rapid hair cell loss with extended macrophage presence in the cochlea, creating a sterile inflammatory environment. Although the early recruitment of m...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/13/7343 |
| _version_ | 1797479595823333376 |
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| author | Liana Sargsyan Austin R. Swisher Alisa P. Hetrick Hongzhe Li |
| author_facet | Liana Sargsyan Austin R. Swisher Alisa P. Hetrick Hongzhe Li |
| author_sort | Liana Sargsyan |
| collection | DOAJ |
| description | Combining aminoglycosides and loop diuretics often serves as an effective ototoxic approach to deafen experimental animals. The treatment results in rapid hair cell loss with extended macrophage presence in the cochlea, creating a sterile inflammatory environment. Although the early recruitment of macrophages is typically neuroprotective, the delay in the resolution of macrophage activity can be a complication if the damaged cochlea is used as a model to study subsequent therapeutic strategies. Here, we applied a high dose combination of systemic gentamicin and furosemide in <i>C57 BL/6</i> and <i>CBA/CaJ</i> mice and studied the ototoxic consequences in the cochlea, including hair cell survival, ribbon synaptic integrity, and macrophage activation up to 15-day posttreatment. The activity of macrophages in the basilar membrane was correlated to the severity of cochlear damage, particularly the hair cell damage. Comparatively, <i>C57 BL/6</i> cochleae were more vulnerable to the ototoxic challenge with escalated macrophage activation. In addition, the ribbon synaptic deterioration was disproportionately limited when compared to the degree of outer hair cell loss in <i>CBA/CaJ</i> mice. The innate and differential otoprotection in <i>CBA/CaJ</i> mice appears to be associated with the rapid activation of cochlear macrophages and a certain level of synaptogenesis after the combined gentamicin and furosemide treatment. |
| first_indexed | 2024-03-09T21:48:02Z |
| format | Article |
| id | doaj.art-7a932662409049808584be66755bb40d |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T21:48:02Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-7a932662409049808584be66755bb40d2023-11-23T20:12:12ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-07-012313734310.3390/ijms23137343Effects of Combined Gentamicin and Furosemide Treatment on Cochlear MacrophagesLiana Sargsyan0Austin R. Swisher1Alisa P. Hetrick2Hongzhe Li3Research Service, VA Loma Linda Healthcare System, Loma Linda, CA 92357, USAResearch Service, VA Loma Linda Healthcare System, Loma Linda, CA 92357, USAResearch Service, VA Loma Linda Healthcare System, Loma Linda, CA 92357, USAResearch Service, VA Loma Linda Healthcare System, Loma Linda, CA 92357, USACombining aminoglycosides and loop diuretics often serves as an effective ototoxic approach to deafen experimental animals. The treatment results in rapid hair cell loss with extended macrophage presence in the cochlea, creating a sterile inflammatory environment. Although the early recruitment of macrophages is typically neuroprotective, the delay in the resolution of macrophage activity can be a complication if the damaged cochlea is used as a model to study subsequent therapeutic strategies. Here, we applied a high dose combination of systemic gentamicin and furosemide in <i>C57 BL/6</i> and <i>CBA/CaJ</i> mice and studied the ototoxic consequences in the cochlea, including hair cell survival, ribbon synaptic integrity, and macrophage activation up to 15-day posttreatment. The activity of macrophages in the basilar membrane was correlated to the severity of cochlear damage, particularly the hair cell damage. Comparatively, <i>C57 BL/6</i> cochleae were more vulnerable to the ototoxic challenge with escalated macrophage activation. In addition, the ribbon synaptic deterioration was disproportionately limited when compared to the degree of outer hair cell loss in <i>CBA/CaJ</i> mice. The innate and differential otoprotection in <i>CBA/CaJ</i> mice appears to be associated with the rapid activation of cochlear macrophages and a certain level of synaptogenesis after the combined gentamicin and furosemide treatment.https://www.mdpi.com/1422-0067/23/13/7343aminoglycosidesloop diureticscochleahair cellsribbon synapsesmacrophages |
| spellingShingle | Liana Sargsyan Austin R. Swisher Alisa P. Hetrick Hongzhe Li Effects of Combined Gentamicin and Furosemide Treatment on Cochlear Macrophages International Journal of Molecular Sciences aminoglycosides loop diuretics cochlea hair cells ribbon synapses macrophages |
| title | Effects of Combined Gentamicin and Furosemide Treatment on Cochlear Macrophages |
| title_full | Effects of Combined Gentamicin and Furosemide Treatment on Cochlear Macrophages |
| title_fullStr | Effects of Combined Gentamicin and Furosemide Treatment on Cochlear Macrophages |
| title_full_unstemmed | Effects of Combined Gentamicin and Furosemide Treatment on Cochlear Macrophages |
| title_short | Effects of Combined Gentamicin and Furosemide Treatment on Cochlear Macrophages |
| title_sort | effects of combined gentamicin and furosemide treatment on cochlear macrophages |
| topic | aminoglycosides loop diuretics cochlea hair cells ribbon synapses macrophages |
| url | https://www.mdpi.com/1422-0067/23/13/7343 |
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