Molecular mechanisms of the opening of the blood-brain barrier in rodents by means of sound

E. Sarantseva, T. Iskra, O. Semyachkina-Glushkovskaya
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Abstract

In this study, in experiments on 35 healthy male mice of the C57BL/6 line weighing 25±3 g, it was shown that loud sound/music for 2 hours causes a temporary increase in the permeability of the blood-brain barrier (BBB) in rodents. To investigate changes in the permeability of the blood-brain barrier, the molecular mechanisms responsible for its discovery were investigated using laser speckle-contrast imaging of regional cerebral blood flow (rCBF), immunohistochemical analysis and biochemical analysis of adrenaline in blood plasma. With a sound-dependent increase in the permeability of the blood-brain barrier, there was a decrease in signal intensity from CLND-5, Occ, JAM and an increase in the signal from ZO-1. However, after 4 hours, the signal intensity from the studied proteins was restored, which may be due to their internalization. The results of the study of the effects of music and sound on of BBB in the intact brain require a revision of traditional knowledge about the barrier functions of the brain and open up new opportunities for non-invasive drug delivery strategies. They also may offer some insight into the etiology of brain disorders that follow inadvertent or deliberate exposure to very loud sounds, i.e. battle or rock concerts.
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通过声音打开啮齿动物血脑屏障的分子机制
本研究以35只体重为25±3g的C57BL/6系健康雄性小鼠为实验对象,结果表明,2小时的大音量音乐可使啮齿动物血脑屏障通透性(BBB)暂时增加。为了研究血脑屏障通透性的变化,我们利用激光散斑对比成像区域脑血流(rCBF)、免疫组织化学分析和血浆肾上腺素生化分析来研究其发现的分子机制。随着声音依赖性血脑屏障通透性的增加,CLND-5、Occ、JAM的信号强度降低,ZO-1的信号强度增加。然而,在4小时后,所研究的蛋白质的信号强度恢复,这可能是由于它们的内化。音乐和声音对完整大脑血脑屏障影响的研究结果要求对大脑屏障功能的传统知识进行修订,并为非侵入性药物递送策略开辟新的机会。它们还可能为无意或故意暴露于非常大的声音(如战斗或摇滚音乐会)后的大脑疾病的病因提供一些见解。
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