A Novel Method to Stimulate Lymphatic Clearance of Beta-Amyloid from Mouse Brain Using Noninvasive Music-Induced Opening of the Blood–Brain Barrier with EEG Markers

O Semyachkina-Glushkovskaya ,Anna Tsven,Dariya Elovenko,Tatyana Iskra,Andrey Terskov,Vasily Ageev,Elena Saranceva,Arina Evsukova,Ali Esmat Sharif,Jürgen Kurths,Valeria Telnova,Ilana Agranovich,Alexander Shirokov,Georgy Karandin,Inna Blokhina,Alexander Khorovodov,Alexander Dubrovsky,Maria O Tsoy ,Nikita A Navolokin ,Ivan V Fedosov ,Alexey N Pavlov

doi:10.3390/app112110287

Abstract

The lymphatic system of the brain meninges and head plays a crucial role in the clearance of amyloid-β protein (Aβ), a peptide thought to be pathogenic in Alzheimer’s disease (AD), from the brain. The development of methods to modulate lymphatic clearance of Aβ from the brain coild be a revolutionary step in the therapy of AD. The opening of the blood–brain barrier (OBBB) by focused ultrasound is considered as a possible tool for stimulation of clearance of Aβ from the brain of humans and animals. Here, we propose an alternative method of noninvasive music-induced OBBB that is accompanied by the activation of clearance of fluorescent Aβ (Fαβ) from the mouse brain. Using confocal imaging, fluorescence microscopy, and magnetic resonance tomography, we clearly demonstrate that OBBB by music stimulates the movement of Fαβ and Omniscan in the cerebrospinal fluid and lymphatic clearance of Fαβ from the brain. We propose the extended detrended fluctuation analysis (EDFA) as a promising method for the identification of OBBB markers in the electroencephalographic (EEG) patterns. These pilot results suggest that music-induced OBBB and the EDFA analysis of EEG can be a noninvasive, low-cost, labeling-free, clinical perspective and completely new approach for the treatment and monitoring of AD.

Highlights

Introduction conditions of the Creative CommonsCerebrospinal fluid (CSF) plays an important role in the movement of nutrients and waste products via the perivascular spaces (PVSs) [1,2,3,4]
Using confocal imaging and magnetic resonance tomography (MRI), we clearly demonstrate that OBBB by music stimulates the movement of Fαβ and Omniscan in CSF
Our results clearly show that music caused OBBB for EBAC in mice 1 h after music action that was associated by an accumulation of EBAC in the brain parenchyma vs. intact mice

Summary

Introduction

Cerebrospinal fluid (CSF) plays an important role in the movement of nutrients and waste products via the perivascular spaces (PVSs) [1,2,3,4]. The (re)discovery of the meningeal lymphatic vessels (MLVs) has led to a reassessment of the pathways for the clearance. The role of MLVs in brain functions, in the context of ageing and Alzheimer’s disease (AD), has been actively studied [7]. Alzheimer’s disease is the most common form of dementia, and its prevalence increases with age [8,9]. Demonstrated that fluorescent-tagged Aβ (Fαβ) is transported along PVSs and the glymphatic pathway, which can remove Fαβ from the CNS [1]

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Conclusion