Yukihiro Masuda

Therapeutic effect of edaravone on inner ear barotrauma in the guinea pig

Inner ear barotrauma (IEB) that is caused by acute pressure changes can often lead to permanent severe sensorineural hearing loss (SNHL). However, the mechanism that causes IEB is still unknown. In the current study, we assessed the involvement of reactive oxygen species (ROS) in IEB and the therapeutic effect of 3-methyl 1-phenyl-2-pyrazolin-5-one (edaravone), which is a free radical scavenger. To create the IEB model, guinea pigs were subjected to quick pressure changes that resulted in acute SNHL. The animals were then divided into two groups, an edaravone-treated IEB group and a non-treated IEB group that only received normal saline. Immunohistochemical analyses for 8-hydroxy-2-deoxyguanosine (8-OHdG) and 4-hydroxy-2-nonenal (4-HNE) were performed to examine the amount of oxidative DNA damage and lipid peroxidation that occurred in guinea pig cochlea. To assess the curative efficacy of edaravone, auditory brainstem response (ABR) testing was performed to evaluate auditory function. Strong immunoreactivities against 8-OHdG and 4-HNE were observed in the inner ear tissues of the non-treated IEB group. Lesser amounts of immunoreactivity were observed in the same region of the edaravone-treated IEB group as compared to the non-treated IEB group. Furthermore, ABR measurement revealed that there was a faster improvement in the threshold shift for the edaravone-treated IEB group as compared to that of the non-treated IEB group. At the final 7-week time point, the threshold shift for the edaravone-treated IEB group was significantly smaller as compared to the non-treated IEB group. These results strongly suggest that ROS is produced in the cochlea in response to acute pressure changes and that ROS plays an important role in the pathophysiology of IEB. Furthermore, edaravone treatment had a therapeutic effect on IEB-induced acute SNHL and thus, edaravone might possibly be able to be used as a therapeutic treatment for IEB.

Vocal fold injury following endotracheal intubation.

Vocal fold scarring results in the formation of fibrous tissue which disturbs the vibratory pattern of the fold during phonation. However, vocal fold scarring in humans is poorly understood because of the lack of clear case reports focusing on voice quality. The authors present a case of vocal fold scarring with changes in voice quality. At the time of injury the pedicle mucosa was cemented with fibrin glue. Phonation was inhibited for two weeks and tranilast (300 mg/day) was given for 3 months. Sixty-nine days later, perceptual evaluation showed a normal result and the phonation time became better, but the mucosal vibration was still lacking. Ninety-seven days later, mucosal vibration was finally restored. We suggest that characterization of vocal fold scarring in humans may be different from that in animals, and recommend that surgical management should be avoided for at least three months after injury.

Protective effect of edaravone in inner-ear barotrauma in guinea pigs

OBJECTIVE The purpose of this study was to determine the protective effect of edaravone, a free radical scavenger, on inner-ear barotrauma (IEB) in guinea pigs, based on a hypothesis implicating free radicals in the development of IEB. MATERIALS AND METHODS One hundred and twenty-five guinea pigs were divided into a control group and a pretreatment group. After auditory brainstem response (ABR) testing, the pretreatment group received 9.0 mg/kg intraperitoneal edaravone. Animals were exposed to pressure loading and then to further ABR testing. RESULTS The incidence of IEB was 62.7 per cent in the control group and 42.9 per cent in the pretreatment group (p<0.01). The distributions of threshold elevation in the control group were 37.3 per cent (for 10 dB or less), 21.3 per cent (for 20-30 dB), 18.0 per cent (for 40-60 dB) and 23.4 per cent (for 70 dB or more), and those in the pretreatment group were 57.1 per cent, 19.1 per cent, 14.3 per cent and 9.5 per cent, for the same respective decibel levels (p<0.01). CONCLUSIONS These results suggest that protective treatment with edaravone can significantly reduce both the incidence of IEB and the severity of the resultant ABR threshold elevation.