Poster abstracts
Poster number 98 submitted by Ben Seicol
Inactivation of Cochlear Macrophages by Minocycline Ameliorates Noise Induced Hearing Loss in CBA/CaJ Mice
Benjamin J. Seicol (Department of Neuroscience, College of Medicine), Meijian Wang (Department of Otolaryngology, College of Medicine), Shengyin Lin (Department of Otolaryngology, College of Medicine), Zixu Guo (Department of Neuroscience, College of Medicine), Katy Garrity (Department of Neuroscience, College of Medicine), Ruili Xie (Department of Otolaryngology, College of Medicine)
Abstract:
Cochlear macrophages are resident immune cells that mediate inflammation in the peripheral auditory system. Activation of cochlear macrophages can worsen damage to sensory hair cells following noise exposure (NE). Immediately after NE, cochlear inflammation occurs and continues for days reaching a maximum between 2-3 days later. The resolution of inflammation is an active process that promotes tissue repair and regeneration. In this study, we sought to test the hypothesis that inactivation of macrophages with minocycline treatment during the pro-inflammatory phase of cochlear inflammation would improve ABR thresholds in CBA/CaJ mice after NE. To test this hypothesis, mice were either given minocycline or vehicle for 5 consecutive days beginning 1 hour before 2 hours of 112 dB or 98 db broad-band noise. Untreated and unexposed mice were also tested as a baseline control. Hearing status was evaluated at 2 weeks after NE. 112 dB noise resulted in a permanent increase of approximately 40 dB in auditory brainstem response (ABR) threshold to clicks in vehicle treated mice at two weeks post NE compared with unexposed controls. Treatment with minocycline, however, reduced ABR threshold shifts to clicks by approximately 15 dB compared with vehicle treatment in mice. NE of 98 dB resulted in no permanent threshold shift, however did lead to approximate 50% fewer hair cell synapses in vehicle treated mice. This synapse loss, or cochlear synaptopathy, was not ameliorated by treatment with minocycline. These results confirm that reducing the pro-inflammatory activity of cochlear macrophages with minocycline treatment ameliorates noise induced hearing loss in mice depending on noise intensity. Better understanding the contribution of cochlea macrophage activation to the progression of hearing loss following NE will allow for the development of treatments that promote the resolution of inflammation to improve outcomes for patients with hearing loss.
Keywords: Macrophages, Noise-induced Hearing Loss, Cochlear Synapses