Time course of cochlear injury discharge (excitotoxicity) determined by ABR monitoring of contralateral cochlear events

Abstract

The dynamics of cochlear excitotoxicity can be monitored from effects on the contralateral ear. After unilateral mechanical ablation of the cochlea (in a mouse model) we observed immediate elevations in auditory brainstem evoked response (ABR) thresholds in the contralateral ear. Threshold elevations peaked at 2–3 h post ablation, and returned to baseline levels after 5–6 h. These contralateral effects are initiated by cochlear afferent injury discharges most likely activating the olivocochlear efferent system. Six hours after cochlear injury, ABR thresholds were fully returned to pre-lesion baseline levels and remained normal for up to 10 days of monitoring. We have confirmed that our cochlear ablation procedure increases short-term activity levels in the auditory brainstem and midbrain using c-fos labelling. The study provides insight into the dynamics of glutamate excitotoxicity, a pathological process directly related to acute tinnitus after acoustic trauma, and more generally implicated in many types of brain injury and neuro-degenerative disease.