Abstract:
Noise-induced hearing loss (NIHL) results from sensory hair cell loss, synaptic damage and the loss of spiral ganglion neurons in the cochlea due to acoustic overstimulation. Hearing loss management is limited to hearing aids and cochlear implants. Previous studies have pointed at the purinergic signalling pathway (particularly adenosine A1 receptor) as a potential treatment option to mitigate NIHL. This study investigated the rescue effects of istradefylline (adenosine A2A receptor antagonist) using functional and histological measurements. Methods: Auditory function was measured in Wistar rats using tone pip (4-32kHz) auditory brainstem responses (ABR) prior to and 14 days post-traumatic noise exposure (8-16kHz, 110 dB SPL, 2 hours). Istradefylline was delivered to the cochlear round window intratympanically using poloxamer-407 gel 24 hours after noise exposure. Functional ABR measurements were cross correlated with quantitative histological analysis of sensory hair cell loss and loss of afferent synapses. Results: Intratympanic administration of istradefylline 24 hours post-exposure did not significantly improve the ABR thresholds, and suprathreshold responses, or the number of sensory hair cells. However, istradefylline administration did result in a significantly higher number of the inner hair cell ribbon synapses in the middle and basal regions of the cochlea. These findings suggest an in vivo neuroprotective effect of istradefylline in the cochlea, but further studies are needed to determine the mechanism of action of istradefylline.