The long term objectives of the proposed research is to improve our current understanding of the role of inflammation in repair and recovery of inner ear structure and function after acoustic injury.
The specific aims are 1) investigate the effect of noise on monocyte migration and proliferation in the inner ear 2) determine which cytokines are produced and where they are produced after noise injury, and 3) determine if the outcome of noise exposure is altered if monocytes migration is inhibited. This proposed research pertains to the treatment and prevention of hearing loss, not only in cases of acoustic trauma, but in other forms of hearing loss that are thought to be part, induced by inflammation and are responsive to immunosuppressive therapies, such as immune-mediated inner ear disease, viral labyrinthitis, or sudden onset hearing loss. The research design involves exposing inbred mice to octave band noise and identifying the cell types that are recruited from the immune system in response to tissue injury. Following identification and quantification of these cells, proliferation of macrophages and monocytes in the auditory periphery will be assessed using BrdU staining. Next, the cytokines that are elaborated by these cells will be measured using quantitative PCR for IL-1, IL-6 and TNF in the inner ear. Once the endogenous population of macrophages has been well described, knock-out mice that are deficient in macrophage migration will be tested for their response to acoustic injury. Methods used for this project include quantitative morphometry, auditory brainstem response testing, immunocytochemistry and quantitative PCR of the mouse cochlea.
| Hirose, Keiko; Sato, Eisuke (2011) Comparative analysis of combination kanamycin-furosemide versus kanamycin alone in the mouse cochlea. Hear Res 272:108-16 |
| Sato, Eisuke; Shick, H Elizabeth; Ransohoff, Richard M et al. (2010) Expression of fractalkine receptor CX3CR1 on cochlear macrophages influences survival of hair cells following ototoxic injury. J Assoc Res Otolaryngol 11:223-34 |
| Sato, Eisuke; Shick, H Elizabeth; Ransohoff, Richard M et al. (2008) Repopulation of cochlear macrophages in murine hematopoietic progenitor cell chimeras: the role of CX3CR1. J Comp Neurol 506:930-42 |
| Sautter, Nathan B; Shick, Elizabeth H; Ransohoff, Richard M et al. (2006) CC chemokine receptor 2 is protective against noise-induced hair cell death: studies in CX3CR1(+/GFP) mice. J Assoc Res Otolaryngol 7:361-72 |
| Hirose, Keiko; Discolo, Christopher M; Keasler, Jodi R et al. (2005) Mononuclear phagocytes migrate into the murine cochlea after acoustic trauma. J Comp Neurol 489:180-94 |
