Objective: To establish a model of ototoxicity in guinea pigs with acoustically evoked short latency negative response (ASNR) and verify the responsible organ of ASNR based on microscopic characteristics of basal membranes, saccules, utricles and ampulla canalis semicircularis of the inner ear.
Methods: Total of 45 guinea pigs were employed in the experiment, which were randomly divided into the control group (15 subjects, 30 ears) and the deafened group (30 subjects, 60 ears). Each animal experienced auditory brainstem response (ABR). A quick treatment was employed for deafened group consisting of a subcutaneous injection of kanamycin at a dose of 400 mg/kg followed by jugular vein injection of ethacrynic acid at a dose of 40 mg/kg one hour later. The animals were performed ABR test from 7 to 10 days after the drug administration. The deafened group was further divided into ASNR group and non-ASNR group based on the presence of ASNR. All the guinea pigs were sacrificed after ABR tests. The Corti organ, macula sacculi, macula utriculi and crista ampullaris were observed by light microscope.
Results: In the deafened group (60 ears), 3 subjects died postoperatively, 27 subjects (54 ears) provided full data. ASNR was elicited in 19 ears (35.2%, 19/54), the thresholds of ASNR were from 110 to 125 dBSPL with average of (121.7 ± 4.5) dBSPL. ASNR latency ranges were 1.80 - 2.08 ms, the average latency of thresholds were (1.93 ± 0.07) ms. The stretched preparation results: overall hair-cell density of macula saccule, macula utriculi and crista ampullaris decreased in order of normal control group, ASNR group and non-ASNR group. There was no difference between the normal group and ASNR group for cell density of macula saccule. Apart from this, statistical differences were found among other groups.
Conclusions: The present study evoked ASNR in an ototoxicity guinea pig model which was profound hearing loss with normal saccular function and normal saccular hair cell density. It suggested that ASNR originates from the saccule and have no relation with cochlear, utricle and semicircular canal according to morphological study.