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
, Alexander Khorovodov 2, Ivan Fedosov 2, Alexey Pavlov 2, Alexander Shirokov 2,3, Ali Esmat Sharif 2, Alexander Dubrovsky 2, Inna Blokhina 2, Andrey Terskov 2, Nikita Navolokin 2,4,5, Arina Evsukova 2, Georgy Karandin 2, Dariya Elovenko 2, Maria Tzoy 2, Vasily Ageev 2, Ilana Agranovich 2, Valeria Telnova 2, Anna Tsven 2, Elena Saranceva 2, Tatyana Iskra 2 and add
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Round 1
Reviewer 1 Report
Some parts of the text have a different format.
Author Response
We would like to express our gratitude to the reviewer for working with our article and a positive assessment of our results.
We made a correction to the text format in the article.
Authors
Reviewer 2 Report
In this manuscript, the authors have examined using music-induced opening of the BBB to enhance the lymphatic clearance of abeta from the mouse brain. In addition, they also showed that EDFA analysis of EEG can be a non-invasive, low-cost monitoring of the Abeta clearance process.
The technical procedure was adequately described, and the given results were supportive of the conclusions.
While music-induced OBBB can be applied to AD patients after modifying the application method, but I am unsure on the monitoring tool.
What is the sample size for each of the different animal groups used in the analysis? Can the authors include this information in figure 1?
Minor typo, for example line 79; "In our preliminary studies, we have demonstrated....".
Author Response
Comment: In this manuscript, the authors have examined using music-induced opening of the BBB to enhance the lymphatic clearance of abeta from the mouse brain. In addition, they also showed that EDFA analysis of EEG can be a non-invasive, low-cost monitoring of the Abeta clearance process. The technical procedure was adequately described, and the given results were supportive of the conclusions.
What is the sample size for each of the different animal groups used in the analysis? Can the authors include this information in figure 1?
Response: We would like to express our gratitude to Reviewer for the positive and helpful comments. We highly appreciate you taking the time out to share your experience with us and work with our manuscript.
We made correction of Figure 1 and added scale bars indication the sample size.
Comment: Minor typo, for example line 79; "In our preliminary studies, we have demonstrated....".
Response: All typos in manuscript were corrected.
Comment: While music-induced OBBB can be applied to AD patients after modifying the application method, but I am unsure on the monitoring tool.
Response: Our article shows that the opening of BBB is accompanied by an increase in the drainage function of the brain. Along with the cerebrospinal fluid, unbound Aβ can be excreted from the brain, which was also shown in the work of Lipsman et al. using FUS in patients with AD (doi.org/10.1038/s41467-018-04529-6. We hypothesize that the music-induced increase in the BBB permeability may be an alternative new method of non-invasive and reversible BBB opening, which can be assessed using MRI with or without contrast (doi: 10.1002/mrm.28687). A PET/MRI scan can be used for simultaneous analysis of BBB permeability and the efficacy of Aβ clearance from brain tissue in patients with AD. We added this discussion in Conclusion.
We would like to thank again Reviewer for the great support and helpful advices in improving of our manuscript.
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