Direct round window membrane application of Dexamethasone in the protection of the guinea pigs' cochlea against irradiation damage

Abstract

Objective To investigate the protective effect of dexamethasone applied to round window membrane (RWM) against radiation-induced inner ear damage in guinea pigs, in order to provide the evidence for preventing and treating radiation-induced inner ear damage. Methods 130 guinea pigs were randomly divided into four groups. (1) Dexamethasone group( n = 45): The guinea pigs were injected with dexamethasone through an intact RWM on right ear for one time after being treated with 70 Gy ~(60)Co γ irradiation. (2) Irradiation group(n = 45) : The guinea pigs were treated with 70 Gy ~(60)Co γ irradiation. (3) Saline group (n = 30): Applying of normal saline through an intact RWM on right ear for one time after being treated with 70 Gy ~(60)Co γ irradiation. (4) Control group(n =45) : Auditory brainstem response (ABR) was tested before the 3 rd day, the second week and the second month after irradiation (treatment) in the first three groups. The animals were sacrificed right after the ABR test and the middle ear mucosa was observed simultaneously. The hair cells were observed by surface preparation of the basilar membrane and scanning electron microscope ( SEM). ResultsThe normal ABR threshold is (8.2 ±2.8) dB. The ABR thresholds increased in those of the three groups treated with irradiation and were rising with time. At the 3rd day, the second week and the second month, ABR thresholds of the dexamethasone group were (24.0 ± 14.1), (27.1±9.9) and (38.0 ± 15.1) dB, respectively, while the irradiation group were (24.5 ± 13.5), (39.5 ± 15.4) and (57.2 ± 18.4) dB. The saline group were (27.0 ± 14.6) and (42.8 ± 13.5) dB, respectively. ABR thresholds of the dexamethasone group at the second week and the second month both decreased compared with those of the irradiation group and saline group ( P < 0.05) . In the control group, the outer hair cell lost by 8.0 ± 2.7 and inner hair cell by 3.7 ± 1.2. The lost quantities of the inner hair cells and outer hair cells were decreased significantly in the three groups with irradiation, and outer hair cells were more than inner hair cells. The loss of hair cells was increased gradually in all groups with irradiation. At the second week and the second month, the loss of outer hair cells in the dexamethasone group were less than those in irradiation group, which were 30.7±7.6 vs. 60.3 ± 14.5 and 67.3 ± 7.0 vs. 100.0 ±5.3 (P < 0.05) . The SEM showed the fusion, loss, lodging and other pathological changes in stereociliary bundle and the losses of hair cell, which were more serious. Those of pathological changes in the dexamethasone group were weaker than those in the groups with irradiation at the 3rd day and the second week. Conclusions Application of dexamethasone through intact RWM could reduce the extent of radiation-induced inner damage. Key words: Dexamethasone; Round window membrane; γ-irradiation; Cochlea