Phenomenon of music-induced opening of the blood-brain barrier in healthy mice

Music plays a more important role in our life than just being an entertainment. For example, it can be used as anti-anxiety therapy of human and animals. However, the unsafe listening of loud music triggers hearing loss in millions of young people and professional musicians (rock, jazz, and symphony orchestra) due to exposure to damaging sound levels using personal audio devices or at noisy entertainment venues including nightclubs, discotheques, bars, and concerts. Therefore, it is important to understand how loud music affects us.

In this pioneering study on healthy mice, we discover that loud rock music below the safety threshold causes opening of the blood-brain barrier (OBBB), which plays an vital role in protecting the brain from viruses, bacteria and toxins. We clearly demonstrate that listening loud music during 2 hrs in an intermittent adaptive regime is accompanied by delayed (1h after music exposure) and short-lasting (during 1-4 hrs) OBBB to low and high molecular weight compounds without cochlear and brain impairments. We present the systemic and molecular mechanisms responsible for music-induced OBBB. Finally, a revision of our traditional knowledge about the BBB nature and the novel strategies in optimizing of sound-mediated methods for brain drug delivery are discussed.

音乐在人类生活中的价值远超娱乐范畴。例如，它可被应用于人类与动物的抗焦虑治疗。然而，不安全的大音量聆听行为，会因使用个人音频设备或身处夜店、迪斯科舞厅、酒吧、音乐会等嘈杂娱乐场所而暴露于损伤性声级，进而导致数百万年轻人及职业音乐人（摇滚、爵士及交响乐团从业者）出现听力损失。因此，阐明大音量音乐对人体的影响机制具有重要意义。

本项针对健康小鼠的开创性研究发现，低于安全阈值的大音量摇滚乐可引发血脑屏障（blood-brain barrier, BBB）开放（OBBB）——血脑屏障本可保护大脑免受病毒、细菌及毒素的侵害。本研究明确证实，采用间歇性适应方案聆听2小时大音量音乐时，会在音乐暴露后1小时出现延迟性、且持续1-4小时的血脑屏障开放，该开放可允许低分子量与高分子量化合物通过，且未伴随耳蜗与大脑损伤。本研究阐明了音乐诱导血脑屏障开放的系统性与分子层面机制。最后，本文对我们关于血脑屏障本质的传统认知进行了修正，并探讨了优化声介导脑部药物递送手段的全新策略。