建立具有正常听性脑干反应阈值特征的GPIAS定义耳鸣样行为动物模型

文献信息

中文摘要

背景： 噪声诱导的耳鸣模型可能包含听力损失和其他听觉改变，从而使行为学指标的解释复杂化。我们表征了一种候选暴露范式，该范式与GPIAS定义的耳鸣样行为相关，且第14天ABR阈值与基线无显著差异。
方法： 一个由100只雄性Sprague-Dawley大鼠组成的常模队列接受重复GPIAS测试，以建立GPIAS定义耳鸣样行为的判定标准。另设独立队列双侧暴露于100-120 dB SPL白噪声2小时，并使用所得0.34截断值进行分类。通过ABR、DPOAE以及耳蜗CtBP2突触前带的免疫荧光评估听觉和形态学改变。分析前对每只大鼠的双侧听觉测量值取平均。
结果： 第14天时，100或105 dB SPL下ABR阈值与基线无显著差异，但在110 dB SPL后12 kHz、115 dB SPL后8 kHz以及120 dB SPL后全部六个频率仍升高。105 dB SPL下的发现包括持续性GPIAS定义耳鸣样行为、第14天8 kHz波I振幅降低，以及无明显外毛细胞丢失。第14天时，耳鸣亚组CtBP2阳性斑点面积较对照组和非耳鸣亚组更小，且每个内毛细胞的斑点数量更少。
结论： 双侧暴露于105 dB SPL白噪声2小时提供了一种候选范式，该范式与GPIAS定义的耳鸣样行为及符合隐性听力损失的听觉特征相关，支持进一步开展与常规听力图正常的耳鸣相关的机制和治疗研究。

英文摘要

BACKGROUND: Noise-induced tinnitus models can include hearing loss and other auditory changes that complicate interpretation of behavioral measures. We characterized a candidate exposure paradigm associated with GPIAS-defined tinnitus-like behavior and no significant day-14 ABR threshold differences from baseline.
METHODS: A normative cohort of 100 male Sprague-Dawley rats underwent repeated GPIAS testing to establish a criterion for GPIAS-defined tinnitus-like behavior. Separate cohorts were exposed bilaterally to 100-120 dB SPL white noise for 2 h and classified using the resulting 0.34 cutoff. ABR, DPOAEs, and cochlear immunofluorescence for CtBP2 presynaptic ribbons assessed auditory and morphological changes. Bilateral auditory measurements were averaged within each rat before analysis.
RESULTS: On day 14, ABR thresholds did not differ significantly from baseline at 100 or 105 dB SPL but remained elevated at 12 kHz after 110 dB SPL, 8 kHz after 115 dB SPL, and all six frequencies after 120 dB SPL. Findings at 105 dB SPL included persistent GPIAS-defined tinnitus-like behavior, reduced day-14 wave-I amplitude at 8 kHz, and no evident outer hair cell loss. On day 14, the tinnitus subgroup showed smaller CtBP2-positive punctum areas and fewer puncta per inner hair cell than controls and the non-tinnitus subgroup.
CONCLUSIONS: Bilateral exposure to 105 dB SPL white noise for 2 h provides a candidate paradigm associated with GPIAS-defined tinnitus-like behavior and auditory features consistent with hidden hearing loss, supporting further mechanistic and therapeutic studies relevant to tinnitus with normal conventional audiograms.