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Contract number
075-15-2019-1885, 075-15-2022-1094
Time span of the project

As of 01.11.2022

Number of staff members
scientific publications
Objects of intellectual property
General information

Name of the project: Discovery of fundamental mechanisms of sleep for breakthrough technologies of neurorehabilitation medicine.

Goals and objectives

Project objective: Creation of a world-class «smart sleep» research laboratory for pioneering research of mechanisms underlying the phenomenon removal of toxins from brain tissue during sleep, creation of new scientific concepts in human and animal anatomy and physiology concerning structure and functions of cerebral lymphatic vessels as a drainage and cleaning system of the brain and characteristic properties of its nocturnal activity and development of breakthrough portable smart technologies to control regenerative properties of sleep for neurorehabilitation medicine

The practical value of the study

Scientific results:

  • We have obtained new scientific data on the activation of the drainage function of the brain in sleep that we obtained using optical coherence tomography, gold nanorods as contrast agents, the technology of optical clearing of the cranial bone and EEG monitoring.
  • New scientific information has been obtained concerning efficient nonlinear methods of frequency and amplitude analysis of electroencephalography, electromyography, electrooculography and electrocardiography data, as well as methods of image recognition by artificial neural networks for the highly-selective detection of slow sleep waves synchronized with the activation of the drainage function of the brain.
  • We have developed a mathematical model that describes the adaptation of the motion of extracellular and perivascular fluids into the meningeal lymphatic system during sleep.
  • New scientific information has been obtained concerning the role of the lymphatic system in the cleaning function of the brain during sleep and age-related changes of these processes.
  • New scientific information has been obtained concerning the functional relation between the increase in the permeability of the hematoencephalic barrier (HEB) and the activation of the cleaning function of the brain in sleep.
  • A breakthrough technology has been developed for the diagnostics of the state of the HEB from data of nonlinear analysis of nocturnal EEG patterns.
  • New scientific information has been obtained concerning the lymphatic cleansing of tissues of a sleeping brain from beta-amyloid and blood products using animal models of the Alzheimer’s disease and neonatal intracranial hemorrhage respectively.
  • The Laboratory has developed a telemetry system for monitoring intracranial pressure and simultaneous recording of EEG in rodents.
  • We have obtained pioneering data on the anatomic relation between meningeal and peripheral lymphatic vessels of the head and the neck of humans and rodents of various ages.
  • The Laboratory has developed a mathematical model of the glial regulation of flow of interstitial fluid during sleep.
  • We have created new methods of functional cartography and three-dimensional functional imaging of the network of lymphatic vessels of the brain and its linings in mice/rats and humans.
  • New scientific information has been obtained concerning the efficiency of the use of the technologies of nonlinear frequency and amplitude analysis of EEG, EMG, EOG and ECG data developed at the first stage under conditions of pathology, including methods of image recognition by neural networks to determine slow sleep waves (on examples of the Alzheimer’s disease and neonatal hemorrhages).
  • We have developed software and an automated stations based on machine learning methods to determine slow sleep waves in the norm and pathology in the moment when   «therapeutic windows of sleep» open.
  • New scientific information has been obtained concerning the possibility of increasing the drainage and cleaning function of the brain by noninvasive stimulation of the «therapeutic windows of sleep» found at the second stage of the project, which manifest themselves in slow wave activity of the brain.
  • We have developed technologies for detecting deep sleep stages in the first days after birth and photostimulation of the lymphatic drainage of blood from brain tissues of newborn infants with intraventricular hemorrhage. We created software that can automatically provide photo interventions during deep sleep.
  • In clinical tests involving healthy volunteers and patients with cognitive disorders it has been established that noninvasive treatment by exposure to binaural sound is accompanied by changes in the electrophysiological pattern associated with the glymphatic system. We analyzed the impact of sleep deficiency and binaural sound on beta-amyloid content in the blood of healthy volunteers. It was established that sleep deprivation is accompanied by a decrease in the level of beta-amyloid in the blood of test subjects, which indirectly indicates its accumulation in brain tissues and this is in agreement with other results with the use of positron emission tomography.
  • We have studied the mechanisms of photostimulating effects on the drainage and cleaning functions of meningeal lymphatic vessels in mice.
  • The Laboratory has developed a portable device in the form of a cap for the nocturnal therapy of excretion of blood products and toxins from the brains of newborn infants.
  • Our researchers have developed a software and hardware complex for monitoring sleep electroencephalograms (EEG) in rodents, which allows to automatically detect slow sleep stages in real time to start laser therapy of the linings of the brain in this period.
  • We have developed a technology for the photostimulation of lymphatic excretion of blood products from brain tissues in adult and newborn mice.
  • A technology has been created for the nocturnal photostimulation of lymphatic excretion of beta-amyloid from brain tissues of mice.
  • A technology has been developed for the sound stimulation of lymphatic excretion of beta-amyloid from brain tissues in mice.
  • A new approach has been developed to analyzing biomedical systems in EEG records to search for and quantitatively evaluate the oscillation patterns on the basis of continuous wavelet transform.
  • We have researched the coherence of the processes of breathing and the parasympathetic regulation of heart rate for individuals of various age groups in the state of wakefulness, during REM sleep and in deep sleep.
  • A method has been proposed for computing the index of the aggregate percentage of phase synchronization of the components of signals of RR intervals and arterial pressure in the low-frequency range from 0.05 to 0.15 Hz.
  • New theoretical concepts have been developed concerning sleep as a systemic marker of the state of the HEB. Models were developed that describe the activation of the nocturnal processes of brain tissue drainage and their possible mechanisms.
  • An interactive database has been developed that contains information on the network of lymphatic vessels of the brain and its linings in the form of a 3D atlas with the use of digital technologies of creation of multimedia objects, virtual reality, three-dimensional computer graphics and machine learning.

Implementation of research results:

  1. Russian Federation Patent No. 2766527. Method for stimulating the cleansing function of the lymphatic system of the brain / Oksana V. Semyachkina-Glushkovskaya, Jürgen G. Kurtz, Aleksandr A. Shirokov, Aleksandr P. Khorovodov, Andrey V. Terskov, Aleksandr I. Dubrovskiy, Valeriy V. Tuchin. Ivan V. Fedosov, Aleksey N. Bashkatov. Elina A. Genina, Aysel G. Mamedova, Mariya M. Klimova, Inna A. Blokhina, Nikita D. Lezhnev. Published on 15 March 2022. Bulletin No. 8. 
  2. Russian Federation Patent No. 210873. A device for high-precision measurement of intracranial pressure. Ivan V. Fedosov, Vasily B. Ageyev, Oksana V. Semyachkina-Glushkovskaya. Published on 12 May 2022. Bulletin No. 15.
  3. Russian Federation Patent No. 2781740. A method of detection of the state of deep sleep. Vasily B. Ageyev, Ivan V. Fedosov, Oksana V. Semyachkina-Glushkovskaya. Published on 17 October 2022. Bulletin No. 29.
  4. Russian Federation Patent No. 2740123. Method of laser biomodulation and increase of blood-brain barrier permeability / Valeriy V. Tuchin, Oksana V. Semyachkina-Glushkovskaya, Elina A. Genina, Aleksey N. Bashkatov; Published on 11 January 2021. Bulletin No. 2

Education and retraining of personnel:

  • We have developed and implemented the master’s degree program «Modern technologies of imaging and analysis of living systems».
  • Three advanced training programs have been developed.
  • Two monographs and one textbook have been published.
  • We have conducted an academic internships of two postgraduate students from 22 November to 21 December 2021 at the Interdisciplinary Center of Sleep Medicine of Charité clinic (Berlin).
  • The Laboratory conducted the 1st Winter On-line School on «Brain Clearance Meets Complex Systems».
  • Two Doctor of Sciences dissertations, one PhD thesis and two Candidate of Sciences dissertations have been prepared and defended.
  • 7 bachelor’s degree students, one specialist degree student, 2 master’s degree students have been trained.


  • Interdisciplinary Center of Sleep Medicine of the Charité clinic (Germany): Internships are provided to young researchers with a focus on the research of the use of methods of machine learning and recurrent analysis, which are applied to biomedical data for the classification of states the organism (sleep, wakefulness, assessment of the permeability of the hematoencephalic barrier etc.), as well as predicting the onset of critical states of the organism (onset of pathologies).
  • Cardiovascular Physics Laboratory of the Humboldt University of Berlin (Germany): internships are provided for the Laboratory’s researchers to study the use of nonlinear analysis methods to forecast the development of brain vessel catastrophes, including technologies for the assessment of the state of the hematoencephalic barrier during wakefulness and sleep.
  • Somnology Department of the Charité clinic in Berlin (Germany):internships are organized to train employees of the Laboratory in conducting research of the nature of sleep and detecting early markers of the risk of the development of neurodegenerative diseases on the basis of the use of methods of machine learning and nonlinear dynamics.
  • Biomedical Laboratory of the Huazhong University of Science and Technology in Wuhan (China PR): The Laboratory is conducting joint research to develop technologies for the photocontrol of the lymphatic processes of excretion of unwanted metabolites from brain tissues.
  • University of New Mexico School of Medicine in Albuquerque (USA): conducting joint research of the nocturnal activity of the lymphatic system of the lining of the brain during sleep in healthy volunteers using functional magnetic resonance imaging.
  • V. I. Razumovsky Saratov State Medical University (Russia).
  • Research Center «Symbiosis» of the Institute of Biochemistry and Physiology of Plants and Microorganisms, Russian Academy of Sciences (Russia).
  • International Science and Education Center «Biophotonics» (Russia).
  • Research Institute of Neurosciences and Medicine (Russia).

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Oxana Semyachkina-Glushkovskaya, Ivan Fedosov, Alexander Shirokov, Elena Vodovozov, Anna Alekseev, Alexandr Khorovodov, Inna Blokhina, Andrey Terskov, Aysel Mamedova, Maria Klimova, Alexander Dubrovsky, Vasily Ageev, Ilana Agranovich, Valeria Vinnik, Anna Tsven, Sergey Sokolovski, Edik Rafailov, Thomas Penzel, Jürgen Kurths
Photomodulation of lymphatic delivery of liposomes to the brain bypassing the blood-brain barrier: new perspectives for glioma therapy. Journal of Nanophotonics. 2021, pp. 000010151520210212. https://doi.org/10.1515/nanoph-2021-0212. IF=8.499 (Q1)
Semyachkina-Glushkovskaya, O.; Mamedova, A.; Vinnik, V.; Klimova, M.; Saranceva, E.; Ageev, V.; Yu, T.; Zhu, D.; Penzel, T.; Kurths, J.
Brain Mechanisms of COVID-19-Sleep Disorders. Int. J. Mol. Sci. 2021, 22, 6917. https://doi.org/10.3390/ijms22136917. IF=4.556 (Q1). Has the status of a highly peer-reviewed article in MDPI in 2021.
Anastasiya Runnova, Maksim Zhuravlev, Rodion Ukolov, Inna Blokhina, Alexander Dubrovski, Nikita Lezhnev, Evgeniya Sitnikova, Elena Saranceva, Anton Kiselev, Anatoly Karavaev, Anton Selskii, Oxana Semyachkina-Glushkovskaya, Thomas Penzel & Jurgen Kurths.
Modified wavelet analysis of ECoG-pattern as promising tool for detection of the blood–brain barrier leakage. Scientific Reports 11, 18505 (2021). https://doi.org/10.1038/s41598-021-97427-9. IF= 4.379 (Q1)
Karavaev A.S., Ishbulatov Yu.M., Prokhorov M.D., Ponomarenko V.I., Kiselev A.R., Runnova A.E., Hramkov A.N., Semyachkina-Glushkovskaya O.V., Kurths J., Penzel T.
Simulating dynamics of circulation in the awake state and different stages of sleep using non-autonomous mathematical model with time delay. Front. Physiol., 13 January 2021 | https://doi.org/10.3389/fphys.2020.612787. IF= 4.134 (Q1)
Nadezhda Semenova, Konstantin Segreev, Andrei Slepnev, Anastasia Runnova, Maxim Zhuravlev, Inna Blokhina, Alexander Dubrovsky, Oxana Semyachkina-Glushkovskaya, Jurgen Kurths
Non-invasive analysis of blood-brain barrier permeability based on wavelet and machine learning approaches. Eur. Phys. J. Plus (2021) 136:736 https://doi.org/10.1140/epjp/s13360-021-01715-2. IF= 3.228 (Q1)
Oxana Semyachkina-Glushkovskaya, Dmitry Postnov, Anastasia Lavrova, Ivan Fedosov, Ekaterina Borisova, Vladimir Nikolenko, Thomas Penzel, Jurgen Kurths, Valery Tuchin
Biophotonic Strategies of Measurement and Stimulation of the Cranial and the Extracranial Lymphatic Drainage Function. IEEE Journal of Selected Topics in Quantum Electronics, vol. 27, no. 4, pp. 1-13, July-Aug. 2021, Art no. 7400313, doi: 10.1109/JSTQE.2020.3045834. IF = 4.917 (Q1)
A.N. Pavlov, A.I. Dubrovsky, A.A. Koronovskii Jr., O.N. Pavlova, O.V. Semyachkina-Glushkovskaya, and J. Kurths
Extended detrended fluctuation analysis of EEG signals during sleep and the opening of the blood-brain barrier. Chaos 30, 073138 (2020); https://doi.org/10.1063/5.0011823 (Q1)
Yurii M. Ishbulatov, Tatiana S. Bibicheva, Vladimir I. Gridnev, Mikhail D. Prokhorov, Marina V. Ogneva, Anton R. Kiselev and Anatoly S. Karavaev
Contribution of Cardiorespiratory Coupling to the Irregular Dynamics of the Human Cardiovascular System. Mathematics 2022, 10, 1088. https://doi.org/10.3390/math10071088. IF= 2.84 (Q1)
Semyachkina-Glushkovskaya O., Postnov D., Penzel T., Kurths J.
Sleep as a Novel Biomarker and a Promising Therapeutic Target for Cerebral Small Vessel Disease: A Review Focusing on Alzheimer’s Disease and the Blood-Brain Barrier. Int. J. Mol. Sci. 2020, 21, 6293; doi:10.3390/ijms21176293 (Q1)
патент рф 2766527. способ стимуляции очистительной функции лимфатической системы мозга / о.в. семячкина-глушковская, ю.г. куртц, а.а. широков, а.п. хороводов, а.в. терсков, а.и. дубровский, в.в. тучин, а.н. и.в. федосов, башкатов, е.а. генина, а.т. мамедова, м.м. климова, и.а. блохина, н.д. лежнев. опубл. 15.03.2022. № 8.
Изобретение относится к экспериментальной нейрореабилитационной и неонатальной медицине, а также сомнологии для фотовоздействия на лимфоток оболочек мозга, головы и шеи с целью повышения восстановительных свойств мозга во время сна после перенесенных черепно-мозговых травм, интракраниальных геморрагий, при лечении опухолей и патологий мозга, сопровождающихся накоплением токсинов в центральной нервной системе, в том числе при болезни Альцгеймера и Паркинсона. Способ стимуляции очистительной функции лимфатической системы мозга путём фотовоздействия на лимфатические сосуды, отличающийся тем, что воздействие осуществляют неинвазивно излучением инфракрасного диапазона с мощностью, не превышающего порога фотоповреждения, на зоны расположения лимфатических сосудов оболочек мозга во время стадии глубокого сна на протяжении всего цикла сна, который регистрируют на электроэнцефалограмме, однократно или курсом.
патент рф 210873. устройство высокоточного измерения внутричерепного давления. и.в. федосов, а.б. агеев, о.в. семячкина-глушковская. опубл. 12.05.2022. № 15.
Изобретение относится к медицинской технике, а именно к устройствам измерения внутричерепного давления инвазивным способом с помощью интегральных датчиков давления и специального устройства крепления. Устройство измерения внутричерепного давления лабораторного животного, содержащее платформу, предназначенную для установки на череп животного, с расположенным на ней съемным измерительным датчиком давления, снабженным выходом для подключения к блоку обработки данных, платформа имеет отверстие для соединения датчика с субарохноидальным пространством, отличающееся тем, что платформа снабжена патрубком, размещенным в ее нижней части соосно с отверстием, измерительный датчик закреплен на платформе при помощи винта с возможностью многократного герметичного соединения с субарохноидальным пространством посредством соединения платформы с костью черепа при помощи компаунда, причем устройство снабжено отводом для подключения катетера.
патент рф 2781740. способ детектирования состояния глубокого сна. а.б. агеев, и.в. федосов, о.в. семячкина-глушковская. опубл. 17.10.2022. бюл. № 29.
Изобретение относится к медицинской технике, а именно, к устройствам физиотерапевтического воздействия световым излучением, преимущественно для новорожденных. Устройство для транскраниальной фототерапии в состоянии сна, преимущественно для новорожденных, включающее корпус для размещения на голове пациента и функциональные узлы для облучения и управления процессом фототерапии, отличающееся тем, что корпус выполнен в виде головного убора - текстильной шапочки, в которой выполнены внутренние карманы для размещения функциональных узлов, соединенных гибкими соединительными шинами, при этом узлы имеют корпуса, форма которых и их расположение обусловлены анатомическими и физиологическими особенностями и положением пациента в состоянии сна, а узел для облучения расположен в затылочной части.
патент рф 2740123. способ лазерной биомодуляции и повышения проницаемости гематоэнцефалического барьера / в.в. тучин, о.в. семячкина-глушковская, э.а. генина, а.н. башкатов; опубл. 11.01.2021. бюл. № 2
Изобретение относится к медицине, а именно к методу управления функциональным состоянием мозга, в том числе гемато-энцефалическим барьером (ГЭБ), в частности, к оптическому управлению функциональноо состояния мозга, включая ГЭБ и может быть использовано для малоинвазивного воздействия на клетки и сосуды головного мозга для обеспечения усиленной их проницаемости для патологических продуктов метаболизма и лекарственных препаратов при лечении опухолей мозга, инсультов, мигрени, депрессии, болезни Альцгеймера и других заболеваний головного мозга. Способ лазерной биомодуляции и повышения проницаемости гематоэнцефалического барьера, включающий воздействие лазерного излучения на выбранную область головы, отличающийся тем, что плотность мощности излучения определяют методом Монте Карло по размеру черепа, толщине кожи головы, подлежащих мягких тканей, кости черепа, твердой мозговой оболочки, церебрально-спинальной жидкости, серого и белого вещества мозга из условия обеспечения плотности мощности в области патологии мозга в интервале 5 – 20 мВт/см2, при этом длину волны излучения выбирают в пределах, лежащих в видимом и инфракрасном диапазонах длин волн на линиях поглощения молекулярного кислорода.
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