The effect of caffeine on hearing in a guinea pig model of acoustic trauma.

Caffeine is a widely consumed substance affecting the metabolism of adenosine and cellular metabolism of calcium. Noise also affects these metabolic pathways while inducing hearing loss. The aim of this study was to determine the effect of daily intake of caffeine on hearing loss after an episode of acoustic trauma in guinea pigs. In this pilot study, forty guinea pigs were randomly divided into four groups: group I (control, n=10) received intraperitoneal saline, group II (n=10) received intraperitoneal caffeine (120 mg/kg/day) for 14 days, group III (n=10) was exposed to noise (tone of 6 kHz at 120 dB for one hour) and group IV (n=10) was exposed to noise as group III and received caffeine as group II. Auditory brainstem responses were measured at four different frequencies (8, 16, 20, and 25 kHz) prior to and at intervals of 1h, 3 days, 10 days, and 14 days after the initial treatment. On day 14, morphological analysis was performed to assess the effects of caffeine on acoustic trauma. Aggravated hearing loss was observed in group IV after 10 days of follow-up. After 14 days, one of the four frequencies (8 kHz) tested showed statistically significant greater impairment in hearing (8.2 ± 3.6 dB, p=0.026). Auditory hair cells showed no difference while spiral ganglion cell counts were diminished in group IV (p<0.05). These findings indicate that caffeine may have a detrimental effect on hearing recovery after a single event of acoustic trauma.

Mujica-Mota MA ，Gasbarrino K ，Rappaport JM ，Shapiro RS ，Daniel SJ ... -  《-》

Association of Caffeine and Hearing Recovery After Acoustic Overstimulation Events in a Guinea Pig Model.

Zawawi F ，Bezdjian A ，Mujica-Mota M ，Rappaport J ，Daniel SJ ... -  《-》

Hydrogen-rich saline alleviates experimental noise-induced hearing loss in guinea pigs.

To examine the efficiency of hydrogen-rich saline in the treatment of intensive noise-induced cochlear injury. Forty guinea pigs were assigned to one of four groups: HS+NOISE (i.p. injection hydrogen-rich saline), NS+NOISE (i.p. injection normal saline), NOISE ALONE (noise control), and NO TREATMENT (normal control) groups. The HS+NOISE, NS+NOISE, and NOISE ALONE groups were exposed to intensive noise (4 h at 115 dB SPL noise of 4000±100 Hz). The auditory brainstem response (ABR) was used to examine the hearing threshold in each group. Distortion product otoacoustic emission (DPOAE) was used to examine outer hair cell function. We also examined cochlear morphology to evaluate inner and outer hair cell trauma induced by noise exposure. Hydrogen-rich saline was administered twice daily for 6 days (2.5 ml/kg, i.p.) 24 h after noise exposure. Baseline ABR thresholds and DPOAE values were normal in all groups at the measured frequencies (2, 4, 8, and 16 kHz) before noise exposure. The ABR threshold shift was 50-55 dB across the frequencies tested, and average DPOAE declined in the NOISE ALONE, NS+NOISE, and HS+NOISE groups 24 h after noise exposure. However, the changes in cochlear parameters were different between groups. The HS+NOISE group showed a significantly decreased ABR threshold value as compared with the NS+NOISE or NOISE ALONE group (P<0.01) on day 7. The mean DPOAE recovered to some extent in the three noise exposure groups, but at most frequencies the HS+NOISE group showed significantly increased DPOAE on day 7 as compared with the NS+NOISE group or NOISE ALONE group (P<0.01). Surface Corti organ preparations stained with succinate dehydrogenase (SDH) showed that most outer hair cells (OHCs) were still dropsical and a few were missing 7 days after noise exposure in the NS+NOISE group. Only a few OHCs were slightly dropsical in the HS+NOISE group. The numbers of missing hair cells 7 days after noise exposure were significantly greater in the NOISE ONLY and NS+NOISE groups than the HS+NOISE group (P<0.01). Hydrogen-rich saline can alleviate experimental noise-induced hearing loss in guinea pigs, partially by preventing the death of cochlear hair cells after intensive noise exposure.

Zhou Y ，Zheng H ，Ruan F ，Chen X ，Zheng G ，Kang M ，Zhang Q ，Sun X ... -  《-》

Antioxidant treatment reduces blast-induced cochlear damage and hearing loss.

Exposure to blast overpressure has become one of the hazards of both military and civilian life in many parts of the world due to war and terrorist activity. Auditory damage is one of the primary sequela of blast trauma, affecting immediate situational awareness and causing permanent hearing loss. Protecting against blast exposure is limited by the inability to anticipate the timing of these exposures, particularly those caused by terrorists. Therefore a therapeutic regimen is desirable that is able to ameliorate auditory damage when administered after a blast exposure has occurred. The purpose of this study was to determine if administration of a combination of antioxidants 2,4-disulfonyl α-phenyl tertiary butyl nitrone (HPN-07) and N-acetylcysteine (NAC) beginning 1 h after blast exposure could reduce both temporary and permanent hearing loss. To this end, a blast simulator was developed and the operational conditions established for exposing rats to blast overpressures comparable to those encountered in an open-field blast of 14 pounds per square inch (psi). This blast model produced reproducible blast overpressures that resulted in physiological and physical damage to the auditory system that was proportional to the number and amplitude of the blasts. After exposure to 3 consecutive 14 psi blasts 100% of anesthetized rats had permanent hearing loss as determined at 21 days post exposure by auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE) testing. Animals treated with HPN-07 and NAC after blast exposure showed a significant reduction in ABR threshold shifts and DPOAE level shifts at 2-16 kHz with significant reduction in inner hair cell (IHC) and outer hair cell (OHC) loss across the 5-36 kHz region of the cochlea compared with control animals. The time course of changes in the auditory system was documented at 3 h, 24 h, 7 day and 21 day after blast exposure. At 3 h after blast exposure the auditory brainstem response (ABR) threshold shifts were elevated by 60 dB in both treated and control groups. A partial recovery of to 35 dB was observed at 24 h in the controls, indicative of a temporary threshold shift (TTS) and there was essentially no further recovery by 21 days representing a permanent threshold shift (PTS) of about 30 dB. Antioxidant treatment increased the amount of both TTS and PTS recovery relative to controls by 10 and 20 dB respectively. Distortion product otoacoustic emission (DPOAE) reached a maximum level shift of 25-30 dB measured in both control and treated groups at 3 h after blast exposure. These levels did not change by day 21 in the control group but in the treatment group the level shifts began to decline at 24 h until by day 21 they were 10-20 dB below that of the controls. Loss of cochlear hair cells measured at 21 day after blast exposure was mostly in the outer hair cells (OHC) and broadly distributed across the basilar membrane, consistent with the distribution of loss of frequency responses as measured by ABR and DPOAE analysis and typical of blast-induced damage. OHC loss progressively increased after blast exposure reaching an average loss of 32% in the control group and 10% in the treated group at 21 days. These findings provide the first evidence that a combination of antioxidants, HPN-07 and NAC, can both enhance TTS recovery and prevent PTS by reducing damage to the mechanical and neural components of the auditory system when administered shortly after blast exposure.

Ewert DL ，Lu J ，Li W ，Du X ，Floyd R ，Kopke R ... -  《-》

G-CSF attenuates noise-induced hearing loss.

In this study, we investigated the effects of granulocyte colony-stimulating factor (G-CSF) for the treatment of noise-induced hearing loss (NIHL) in a guinea pig model. Forty guinea pigs were randomly divided into four groups: control, noise (white noise, 3 h/d for 2 days at 115 dB), noise+G-CSF (350 μg/kg/d for 5 days), and noise+saline. Auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE) were used to determine the hearing threshold and outer hair cell function, respectively, in each group. Cochlear morphology was examined to evaluate hair cell injury induced by intense noise exposure. Fourteen days after noise exposure, the noise+G-CSF group had a lower ABR value than the noise group (P<0.05) or the noise+saline group (P<0.01). At most frequencies, the DPOAE value of the noise+G-CSF group showed a significant rise (P<0.05) compared to the noise group or the noise+saline group. Neither the ABR value nor the DPOAE value differed between the noise group and the noise+saline group. The morphology of the phalloidin-stained organ of Corti was consistent with the functional measurements. In conclusion, G-CSF can preserve hearing in an experimental model of NIHL in guinea pigs, by preserving hair cells after intense noise exposure.

Shi ZT ，Lin Y ，Wang J ，Wu J ，Wang RF ，Chen FQ ，Mi WJ ，Qiu JH ... -  《-》