J Korean Med Sci.  2020 Apr;35(13):e81. 10.3346/jkms.2020.35.e81.

Objective Verification of Acute Tinnitus and Validation of Efficacy of Systemic Steroids in Rats

• Kim YC
• Kim H
• Kim YS
• Jung SK
• Park IY
• Choung YH
• Jang JH

• KMID: 2509604
• DOI: http://doi.org/10.3346/jkms.2020.35.e81

Abstract

Background
This study was performed to identify acute tinnitus and evaluate the efficacy of steroids for noise-induced acute tinnitus by measuring the gap-prepulse inhibition of the acoustic startle (GPIAS) value in an animal model.
Methods
Nineteen rats (the noise group [n = 7] and the noise + dexamethasone [DEX] group [n = 12]) were exposed to narrow-band noise centered at 16 kHz from a sound generator for 4 hours. The noise + DEX group received intraperitoneal steroid administration daily for 5 days (1.5 mg/kg/day) after completing noise exposure. Auditory brainstem response and GPIAS value were measured just prior to, and 1 day after noise exposure and on days 1 and 10 days after completing steroid administration. The changes in cochlear structure were evaluated by histological analysis.
Results
The threshold shift was checked 1 and 10 days after intraperitoneal steroid injection, and no differences in threshold shift were observed between the two groups in each frequency except for 32 kHz 1 day after steroid injection. The mean GPIAS value in the noise + DEX group (36.4% ± 14.1%) was significantly higher than that in the noise group (16.4% ± 18.8%) 10 days after intraperitoneal steroid administration (P = 0.017). There were no pathological changes associated with noise trauma in the two groups as determined on hematoxylin and eosin and immunohistochemical staining.
Conclusion
An acute tinnitus model with minimal structural changes by noise exposure was set up, and used to verify tinnitus objectively by measuring the GPIAS value. Steroid therapy for control of tinnitus was validated in this animal model.

Keyword

Tinnitus; GPIAS; Auditory Brainstem Response; Dexamethasone; Noise-Induced Hearing Loss

Figure

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  Fig. 1 Experimental schedules. Nineteen rats were divided into the noise group (n = 7), and noise + DEX group (n = 12) injected intraperitoneally with 1.5 mg of DEX/kg daily for 5 days after completion of noise exposure. GPIAS and ABR were recorded just before and after noise exposure. ABR measurement was repeated 1 and 10 days after completion of DEX administration.DEX = dexamethasone, GPIAS = gap-prepulse inhibition of the acoustic startle, ABR = auditory brainstem response.

• 

  Fig. 2 Components of the GPIAS measurement system and acoustic stimuli used for GPIAS. (A) This system was composed of a soundproof chamber with acoustic stimulator and a startle reflex-sensing enclosure. (B) Implemented PC-based graphical user interface screen for measuring GPIAS values. Schematic view of pulse pattern of (C) gap and no gap.GPIAS = gap-prepulse inhibition of the acoustic startle.

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  Fig. 3 Mean threshold shift of auditory brainstem responses for hearing change. The noise + DEX group showed a significantly larger threshold shift at 32 kHz than the noise group 1 day after DEX administration. Error bars indicate one standard deviation.DEX = dexamethasone.*P < 0.05.

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  Fig. 4 GPIAS. The noise + DEX group showed significantly higher mean GPIAS values than the noise group 10 days after DEX administration. Error bars indicate one standard deviation.GPIAS = gap-prepulse inhibition of the acoustic startle, DEX = dexamethasone.*P < 0.05.

• 

  Fig. 5 Microscopic images with hematoxylin and eosin staining of the cochlea. Hair cells and spiral ganglion neurons in (A) control, (B) noise, and (C) noise + dexamethasone groups. (1) Apical, (2) mid, and (3) basal turns were examined in each group. Scale bars = 25 μm.

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  Fig. 6 Immunohistochemical staining of CtBP2 and MYO7a of the cochlea. (A) Control, (B) noise, and (C and D) noise + dexamethasone groups. CtBP2 was used to label synaptic ribbons using antibodies with red fluorescence. The white dashed region shows the inner hair cell region. Scale bars = 5 µm.

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