Oksana V. Semyachkina-Glushkovskaya is a Russian leader in the study of the lymphatic system of the brain, Deputy Director for commercialization of scientific developments of the SSU Scientific Medical Center, Head of the Department of Physiology and Animals of the Faculty of Biology of SSU. A young research team led by O.V Semyachkina-Glushkovskaya. is the first who laid the foundation for research on the functions of the lymphatic system of the brain in Russia. In the pioneering work of her young team, it was shown that the cerebral lymphatics is a "tunnel" for the elimination of toxins (beta-amyloid, blood products) and unnecessary molecules that enter its tissues through the open blood-brain barrier (BBB) (Zhinchenko, E., Navolokin, N ., Shirokov, A., Khlebcov, B., Dubrovsky, A., Saranceva, E., Abdurashitov A., Khorovodov, A., Terskov A., Mamedova, A., Klimova, M., Agranovich, I., Martinov, D., Tuchin, V., Semyachkina-Glushkovskaya, O., Kurths, J. Pilot study of transcranial photobiomodulation of lymphatic clearance of beta-amyloid from the mouse brain: breakthrough strategies for nonpharmacologic therapy of Alzheimer's disease. 10(8): doi.org/10.1364/BOE.10.004003 (2019); Mariya Ulanova, Natalia Shushunova, Alexander Khorovodov, Ilana Agranovich, Anastasia Bodrova, Madina Sagatova, Ali Esmat Shareef, Elena Saranceva, Tatyana Iskra, Mariya Dvoryatkina, Ekaterina Zhinchenko, Olga Sindeeva, Valery Tuchin, and Jurgen Kurths. Photodynamic opening of the blood-brain barrier and pathways of brain clearing pathways/ J Biophotonics. 2018 11(8):e201700287. doi: 10.1002/jbio.201700287; Semyachkina-Glushkovskaya O., Abdurashitov A., Dubrovsky A., Bragin D., Bragina O., Shushunova N., Maslyakova G., Navolokin N., Bucharskaya A., Tuchin V., Kurths J. Application of optical coherent tomography for in vivo monitoring of the meningeal lymphatic vessels during opening of blood-brain barrier: mechanisms of brain clearing. Journal of Biomedical Optics 2017 Dec;22(12):1-9. doi: 10.1117/1.JBO.22.12.121719; Duarte Torres E.N. , Abdurashitov A.S. , Namykin A.A., Shirokov A.A. , Shushunova N.A., Khorovodov A.P. , Sarantsev E.I. , and Semyachkina-Glushkovskaya O.V. Optical monitoring of the meningeal lymphatic clearance after opening of blood-brain barrier / Proceedings Volume 11067, Saratov Fall Meeting 2018: Computations and Data Analysis: from Nanoscale Tools to Brain Functions; 1106713 (2019) https://doi.org/10.1117/12.2524427; M. Klimova; E. Duarte Torres; E. Saranceva; T. Chukalina; T. Iskra; O. Semyachkina-Glushkovskaya; Ju. Kurths. Lymphatic or glymphatic systems: opposite concepts in fundamental understanding of the brain clearing / Proceedings Volume 11067, Saratov Fall Meeting 2018: Computations and Data Analysis: from Nanoscale Tools to Brain Functions; 110670G (2019) https://doi.org/10.1117/12.2524687; Klimova M/; A. Dubrovsky; E. Duarte Torres; A. Abdurashitov; A. Shirokov; A. Terskov; A. Khorovodov; E. Sarantseva; T. Iskra; O. V. Semyachkina-Glushkovskaya. The role of the meningeal lymphatic in the brain clearing / Proceedings Volume 11067, Saratov Fall Meeting 2018: Computations and Data Analysis: from Nanoscale Tools to Brain Functions; 110670Z (2019) https://doi.org/10.1117/12.2524451). Original experimental approaches have been developed for in vivo study of the lymphatic drainage function of the brain based on the use of optical coherence tomography (Oxana Semyachkina-Glushkovskaya, Vladimir Chehonin, Ekaterina Borisova, Ivan Fedosov, Anton Namykin, ArkadyAbdurashitov, Alexander Shirokov, Boris Khlebtsov, Yelena Lyubun, Nikita Navolokin, Mariya Ulanova Photodynamic opening of the blood-brain barrier and pathways of brain clearing pathways/ J Biophotonics 2018 11(8):e201700287 doi: 10.1002/jbio.201700287; Semyachkina-Glushkovskaya O., Abdurashitov A., Dubrovsky A., Bragin D., Bragina O., Shushunova N. , Maslyakova G., Navolokin N., Bucharskaya A., Tuchin V., Kurths J. Application of optical coherent tomography for in vivo monitoring of the meningeal lymphatic vessels during opening of blood-brain barrier: mechanisms of brain clearing. Journal of Biomedical Optics 2017 Dec;22(12):1-9. doi: 10.1117/1.JBO.22.12.121719). A patent was obtained for the development of a technology for in vivo study of the cleansing function of the lymphatic system of the brain (RF Patent 2703393. A method for visualizing the lymphatic system of the brain using optical coherence tomography in vivo / A.S. Abudrashitov, O.V. Semyachkina-Glushkovskaya; Published on October 16, 2019. Bull. No. 29.). Theoretical foundations of the directions for studying the functions of cerebral lymphatic vessels using special markers of the lymphatic endothelium have been developed (Blood–Brain Barrier, Lymphatic Clearance, and Recovery: Ariadne's Thread in Labyrinths of Hypotheses / Journal: Int. J. Mol. Sci., 2018. Vol. 19 No. 3818. doi: 10.3390/ijms19123818; Semyachkina-Glushkovskaya O.V. Lymphatic system in the meninges: new discoveries in neurophysiology / Siberian Medical Review V.6, P.39-50 (2017)). A deep analysis of the theory of the glymphatic system, which is currently being actively discussed in the international community, was carried out (Iliff, JF; Wang, M.; Liao, Y.; Nedergaard, MA Paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid β Sci Transl. Med. 2012, 4, 147ra111.; Iliff, JJ; Goldman, S.; Nedergaard, M. Clearing the mind: Implications of dural lymphatic vessels for brain function. Lancet Neurol. 2015, 14, 977–979; Iliff, JJ; Nedergaard, M. Is there a cerebral lymphatic system? Stroke 2013, 44, 93–95). Using physiological and biophysical calculations based on mathematical modeling, it was proved that the movement of macromolecules is impossible through glia. Considering the rapid speeds of tracer movement from various areas of the brain, the obvious routes for their removal are the perivascular spaces and the presence of anatomical connections between the cerebral, meningeal, and peripheral lymphatic systems (Blood–Brain Barrier, Lymphatic Clearance, and Recovery: Ariadne's Thread in Labyrinths of Hypotheses / Journal: Int. J. Mol. Sci., 2018. Vol. 19. No. 3818. doi: 10.3390/ijms19123818; M. Klimova; E. Duarte Torres; E. Saranceva; T. Chukalina; T. Iskra; O. Semyachkina- Glushkovskaya, Ju. Kurths, Lymphatic or glymphatic systems: opposite concepts in fundamental understanding of the brain clearing / Proceedings Volume 11067, Saratov Fall Meeting 2018: Computations and Data Analysis: from Nanoscale Tools to Brain Functions; 110670G (2019) https:// doi.org/10.1117/12.2524687).
Preliminary studies have shown that blockade of the outflow of cerebrospinal fluid from the brain through the lymphatic pathways provokes the development of stroke in hypertensive mice (RF Patent 2688798. Method for modeling intracerebral hemorrhages in hypertensive rats / O.V. Semyachkina-Glushkovskaya, A.V. Terskov, M. M. Klimova, A.P. Khorovodov, N.A. Navolokin, D.E. Bragin, A.I. Dubrovsky, Yu.G. Kurtz, Published 01.02.2019, Bull. No. 4).
As part of the projects of the team under the guidance of the project manager (RNF: No. 14-15-00128 (2014-2016); No. 16-15-10252 (2016-2018); No. 17-15-01263 (2017-2019); No. 17- 75-20069 (2017-2019); No. 18-15-00172 (2018-2020)) studies were conducted to study the permeability of the BBB during the development of a stroke, which formed the basis for the idea of studying the relationship between the opening of the BBB and the immediate activation of the lymphatic system of the brain (Oxana Semyachkina-Glushkovskaya, Ekaterina Borisova, Latchezar Avramov, Ivan Fedosov, Anton Namykin, Arkady Abdurashitov, Sergey Serov, Alexey Pavlov, Ekaterina Zinchenko, Vlad Lichagov, Nikita Navolokin, Galina Maslyakova, Dan Zhu, Qingming Luo, Valery Tuchin, Jürgen Kurths. The stress and vascular catastrophes in newborn rats: mechanisms preceding and accompanying the brain hemorrhages // Frontiers in Physiology Vol 7. 2016 doi:10.3389/fphys.2016.00210; 1. Oxana Semyachkina-Glushkovskaya, Alexey Pavlov, Jürgen Kurths, Ekaterina Borisova, Alexander Gisbrecht, Olga Sindeeva, Arkady Abdura shitov, Alexander Shirokov, Nikita Navolokin, Ekaterina Zinchenko, Artem Gekalyuk, Maria Ulanova, Dan Zhu, Qingming Luo, and Valery Tuchin. Optical monitoring of stress-related changes in the brain tissues and vessels associated with hemorrhagic stroke in newborn rats // Biomed Opt Express. 2015 Oct 1; 6(10): 4088–4097.IF=3.648doi: 10.1364/BOE.6.004088; Oxana Semyachkina-Glushkovskaya, Vladimir Chehonin, Ekaterina Borisova, Ivan Fedosov, Anton Namykin, Arkady Abdurashitov, Alexander Shirokov, Boris Khlebtsov, Yelena Lyubun, Nikita Navolokin, Mariya Ulanova, Natalia Shushunova, Alexander Khorovodov, Ilana Agranovich, Anastasia Bodrova, Madina Sagatova, Ali Esmat Shareef, Elena Saranceva, Tatyana Iskra, Mariya Dvoryatkina, Ekaterina Zhinchenko, Olga Sindeeva, Valery Tuchin, and Jurgen Kurths. Photodynamic opening of the blood-brain barrier and pathways of brain clearing pathways/ J Biophotonics. 2018 11(8):e201700287. doi: 10.1002/jbio.201700287).
As part of joint research with partners from the University of Western Australia, a diagnostic computer complex was developed to assess the activity of endothelial and vegetative mechanisms of cerebral microcirculation control ( Alexey N. Pavlov, Arkady S. Abdurashitov, Olga N. Pavlova, Valery V. Tuchin, Olga S. Sindeeva, Sergey S. Sindeev and Oxana V. Semyachkina-Glushkovskaya Hidden stage of intracranial hemorrhage in newborn rats studied with laser speckle contrast imaging and wavelets // Journal of Innovative Optical Health Sciences Vol. 8, No. 5 (2015) 1550041 ( 8 pages); A.N. Pavlov, O.V. Semyachkina-Glushkovskay, V.V. Lychagov, A.S. Abdurashitov, O.N. Pavlova, O.A. Sindeeva, S.S. Sindeev. Multifractal characterization of cerebrovascular dynamics in newborn rats // Chaos, Solitons and Fractals. 2015 77. 6-10).
Original optical approaches have been developed to study the macro- and microcirculation of the brain (Arkady Abdurashitov, Sergey Sindeev, Olga Sindeeva, Oxana V. Semyachkina-Glushkovskaya, Valery V. Tuchina. Off-axis holographic laser speckle contrast imaging of blood vessels in tissues / Journal Biomedical Optics 2017.22(9): 91514. doi: 10.1117/1.JBO.22.9.091514).
New possibilities for the use of photodynamic treatment of glioma have been disclosed and it has been shown that classical protocols for the interaction of a laser and a photosensitizer can also be used to deliver drugs to the brain by a photodynamic increase in the permeability of the BBB (Semyachkina-Glushkovskaya O., Kurths J., Borisova E., Sokolovsky S. ., Mantareva N., Angelov I., Shirokov A., Navolokin N., Shushunova N., Khorovodov A., Ulanova M., Sagatova M., Ahranovich I., Sindeeva O., Gekalyuk A., Bordova A., Rafailov E. Photodynamic opening of blood-brain barrier / Biomedical Optics Express 2017 8(11): https://doi.org/10.1364/BOE.8.005040 Chao Zhang, Wei Feng, Elena Vodovozova, Daria Tretiakova, Ivan Boldyrevd , Yusha Li, Jurgen Kürths, Tingting Yu, Oxana Semyachkina-Glushkovskaya, and Dan Zhu, Photodynamic opening of the blood-brain barrier to high weight molecules and liposomes through an optical clearing skull window, Biomedical Optics Express, 2018, V. 9. No. 10, pp. 4850–4862h ttps://doi.org/10.1364/BOE.9.004850).
Age differences in the photodynamic opening of the BBB have been established (Chao Zhang, Wei Feng, Yusha Li, Jurgen Kürths, Tingting Yu, Oxana Semyachkina-Glushkovskaya, Dan Zhu. Age differences in photodynamic opening of blood-brain barrier through optical clearing skull window in mice / Lasers in Surgery and Medicine. 2019 Sep;51(7):625-633. doi: 10.1002/lsm.23075).
New methods for quantifying BBB permeability have been developed (Wei Feng, Chao Zhang, Tingting Yu, Oxana Semyachkina-Glushkovskaya and Dan Zhu. In vivo monitoring blood-brain barrier permeability using spectral imaging through optical clearing skull window / J Biophotonics. 12(4):e201800330. doi: 10.1002/jbio.201800330).
A method for non-invasive opening of the BBB using loud music and sound has been developed (Semyachkina-Glushkovskaya O. et a. Loud music/sound opens the blood-brain barrier: a readily available approach to brain drug delivery and therapy of brain diseases. Scientific Reports (under review, 2019); Semyachkina-Glushkovskaya O., A. Abdurashitov, A. Pavlov, A. Shirokov, N. Navolokin, O. Pavlova, A. Gekalyuk,M. Ulanova, N. Shushunova, A. Bodrova, E. Saranceva, A. Khorovodov, I. Agranovich, V. Fedorova, M. Sagatova, A. E. Shareef, C. Zhang, D. Zhu and V. Tuchin. Laser speckle imaging and wavelet analysis of cerebral blood flow associated with the opening of the blood–brain barrier by sound. Chinesse Optical Letters. 2017. 15(9), 090002(2017)).
A know-how has been developed and a license has been obtained for a method of effective suppressing the growth of glioma by stimulating the immune and lymphatic drainage mechanisms of the brain based on the action of a new generation 1268 nm laser capable of stimulating the formation of singlet oxygen directly without the use of photosensitizers (Know-How 547-B dated 10/15/2019 " A method for transcranial photodynamic suppression of glioma growth”; O.V.Semyachkina-Glushkovskaya, S.G. Sokolovski, A. Goltsov, A.S. Gekaluyk, O.A. Bragina, E.I. Saranceva, V.V. Tuchin, E.U. Rafailov. Laser-induced generation of singlet oxygen and its role in the cerebrovascular physiology / Progress in Quantum Electronics. 2017, Vol. 55, P.112-128 (IF=11,0). DOI: 10.1016/j.pquantelec.2017.05.001 ).
A patent was obtained for non-invasive opening of the BBB using photodynamic exposure (RF Patent 2688013. A method for non-invasively increasing the permeability of the blood-brain barrier / Yu.G. Kurtz, E.U. Rafailov, V.V. Tuchin, D.E. Bragin, A.B. Salmina, V. V. Salmin, A. A. Shirokov, N. A. Navolokin, E. G. Borisova, M. V. Ulanova, A. V. Morgun, A. A. Bodrova, A. P. Khorovodov, A. A. Shushunova, A. E. Sharif, M. M. Klimova, A. V. Terskov, and A. A. Dubrovsky, published May 17, 2019, Bull. No. 14).
A new model of fluorescent glioma has been developed (RF Patent 2699754. Fluorescent glioma cell line and method for its production / A.A. Shirokov, A.S. Fomin, O.V. Semyachkina-Glushkovskaya.; Published 09.09.2019. Bull. No. 25
Mathematical approaches for diagnosing disorders of the autonomic control of cerebral blood flow in the development of stroke have been developed (Pavlov A., Abdurashitov A, Pavlova P., Ulanova M., Bodrova A., Shushunova N., Khorovodov A., Semyachkina-Glushkovskaya O. Characterization of cerebral blood flow dynamics with multiscale entropy / Journal of Innovative Optical Health Sciences 10(5) (2017) 1743005 (9 pages)).
New methods of stimulating the regenerative processes of the brain based on the use of the method of transcranial anode stimulation and photobiomodulation have been developed. (Bragina O., Lara D., Nemoto E., Shuttleworth C., Semyachkina-Glushkovskaya О., Bragin D. Anodal tDCS improves cerebral blood flow, tissue oxygenation and neurologic outcome in mice after traumatic brain injury // Brain Stimulation – 2017. – Vol. 10, no. 4. – P. 75-76. (Scopus, WoS, IF= 6,120, DOI: 10.1016/j.brs.2017.04.115; Bragina O., Semyachkina-Glushkovskaya O., Yang Y., Nemoto E., Shuttleworth C., Bragin D. Repetitive anodal transcranial direct current stimulation improves outcome at three weeks but not one week after TBI in mice // Journal of Neurotrauma – 2017 – 34(13), P.71-72; Zhinchenko, E., Navolokin, N., Shirokov, A., Khlebcov, B., Dubrovsky, A., Saranceva, E., Abdurashitov A., Khorovodov, A., Terskov A., Mamedova, A., Klimova, M., Agranovich, I., Martinov, D., Tuchin, V., Semyachkina-Glushkovskaya, O., Kurths, J. Pilot study of transcranial photobiomodulation of lymphatic clearance of beta-amyloid from the mouse brain: breakthrough strategies for nonpharmacologic therapy of Alzheimer’s disease. Biomedical Optics Express. 10(8): doi.org/10.1364/BOE.10.004003; Bragina O.A., Semyachkina-Glushkovskaya O.V., Ruzavina A.I., Trofimov A.O., Bragin D.E. Anodic transcranial direct current stimulation increases cerebral blood flow, tissue oxygenation and reduces neurological disorders in mice after traumatic brain injury // Medial. – 2017. – no. 1. - S. 189-190).
Applying an interdisciplinary approach and using the methods of photoacoustics, histology, optical coherence tomography and speckle imaging of cerebral vessels, as well as studying the complexity of blood pressure signals, it was found that cerebral veins are an important informative platform for studying the mechanisms of the pre-stroke state and new therapeutic and prognostic approaches in the treatment of stress-induced intracranial bleeding in the first days after birth (Oxana Semyachkina-Glushkovskaya, Alexey Pavlov, Jürgen Kurths, Ekaterina Borisova, Alexander Gisbrecht, Olga Sindeeva, Arkady Abdurashitov, Alexander Shirokov, Nikita Navolokin, Ekaterina Zinchenko, Artem Gekalyuk, Maria Ulanova, Dan Zhu, Qingming Luo, and Valery Tuchin. Optical monitoring of stress-related changes in the brain tissues and vessels associated with hemorrhagic stroke in newborn rats // Biomed Opt Express. 2015 Oct 1; 6(10): 4088–4097; A.N. Pavlov, O.V. Semyachkina-Glushkovskay, V.V. Lychagov, A.S. Abdurashitov, O.N. Pavlova, O.A. Sindeeva, S.S. Sindeev. Multifractal characterization of cerebrovascular dynamics in newborn rats // Chaos, Solitons and Fractals. 2015 77. 6-10; Alexey N. Pavlov, Arkady S. Abdurashitov, Olga N. Pavlova, Valery V. Tuchin, Olga S. Sindeeva, Sergey S. Sindeev and Oxana V. Semyachkina-Glushkovskaya. Hidden stage of intracranial hemorrhage in newborn rats studied with laser speckle contrast imaging and wavelets // Journal of Innovative Optical Health Sciences Vol. 8, No. 5 (2015) 1550041 (8 pages); 9. Arkady S. Abdurashitov, Vladislav V. Lychagov, Olga A. Sindeeva, Oxana V. Semyachkina-Glushkovskaya, Valery V. Tuchina. Histogram analysis of laser speckle contrast image for cerebral blood flow monitoring// Fronties of Optoelectronics, 2015. DOI 10.1007/s12200-015-0493-z; A.N. Pavlov, O.V. Semyachkina-Glushkovskaya, O.A. Sindeeva, O.N. Pavlova, E.P. Shuvalova, Q. Huang, D. Zhu, P. Li, V. Tuchin, Q. Luo. Cerebral venous dynamics in newborn mice with intracranial hemorrhage studied using wavelets // Proc. of SPIE. Vol. 9322-932214-1. 2015).
