Noise-Induced Hearing Loss in Mice: Effects of High and Low Levels of Noise Trauma in CBA Mice.

Acoustic trauma can induce temporary or permanent noise-induced hearing loss (NIHL). Noise exposed animal models allow us to study the effects of various noise trauma insults on the cochlea and auditory pathways. Here we studied the short-term and long-term functional changes occurring in the auditory system following exposure to two different noise traumas. Several measures of hearing function known to change following noise exposure were examined: Temporary (TTS) and permanent (PTS) threshold shifts were measured using auditory brainstem responses (ABR), outer hair cell function was examined using distortion product otoacoustic emissions (DPOAEs), and auditory temporal processing was assessed using a gap-in-noise (GIN) ABR paradigm. Physiological measures were made before and after the exposure (24 hours, 2 weeks, 4 weeks, and 1 year). The animals were perfused and their brain, and cochlea were collected for future biomarker studies. Young adult mice were exposed to 110 dB and 116 dB octave-band noise levels for 45 minutes, and both groups demonstrated significant threshold shifts 1 day post-noise exposure across all frequencies. However 2 weeks postexposure, PTS within the 110 dB group was significantly reduced compared to 1 day post trauma, this improvement in thresholds was not as great in the 116 dB exposure group. At 2 weeks post-trauma, differences between the measured PTS in the two groups was significant for 4 of the 7 measured frequencies. At this 1 year time point after exposure, mice in the 110 dB group showed very minor PTS, but the 116 dB group showed a large PTS comparable to their 2 and 4 week PTS. At this time point, PTS variation between the two groups was significant across all frequencies. DPOAE amplitudes measured 2 weeks post exposure showed recovery for all frequencies within 10 dB (average) of the baseline in the 110 dB group, however for the 116 dB exposure DP amplitudes were elevated by about 30 dB. The differences in DPOAE amplitudes between the 110 dB and 116 dB groups were significant at 2 weeks, 4 weeks, and 1 year post-trauma in the mid frequency range. At 2 weeks, 4 weeks, and 1 year, DPOAE thresholds returned to within 10 dB of the baseline for the 110 dB group in the low and mid frequency range, whereas the 116 dB group still showed shifts of 30 dB for all frequency ranges. For Gap ABRs, there was a significant decrease in both noise burst 1 (NB1) and noise burst 2 (NB2) amplitudes for peaks 1 and 4 in the 116 dB group relative to the 110 dB group when measured at 1 year post trauma. These results indicate that a 6 dB increase in noise exposure intensity results in a significant increased ototrauma in both the peripheral and central auditory systems.

Impact of mild traumatic brain injury on auditory brain stem dysfunction in mouse model.

The auditory brainstem response (ABR) is an electrophysiological test that examines the functionality of the auditory nerve and brainstem. Traumatic brain injury (TBI) can be detected if prolonged peak latency is observed in ABR measurements, since latency measures the neural conduction time in the brainstem, and an increase in latency can be a sign of pathological lesion at the auditory brainstem level. The ABR is elicited by brief sounds that can be used to measure hearing sensitivity as well as temporal processing. Reduction in peak amplitudes and increases in latency are indicative of dysfunction in the auditory nerve and/or central auditory pathways. In this study we used sixteen young adult mice that were divided into two groups: sham and mild traumatic brain injury (mTBI), with ABR measurements obtained prior to, and at 2, 6, and 14 weeks after injury. Abnormal ABRs were observed for the nine TBI cases as early as two weeks after injury and the deficits lasted for fourteen weeks after injury. Results indicated a significant reduction in the Peak 1 (P1) and Peak 4 (P4) amplitudes to the first noise burst, as well as an increase in latency response for P1 and P4 following mTBI. These results are the first to demonstrate auditory sound processing deficits in a rodent model of mild TBI.