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    Photobiomodulation of lymphatic drainage and clearance: Perspective strategy for augmentation of meningeal lymphatic functions
    (Washington, DC : Optica, 2020) Semyachkina-Glushkovskaya, Oxana; Abdurashitov, Arkady; Dubrovsky, Alexander; Klimova, Maria; Agranovich, Ilana; Terskov, Andrey; Shirokov, Alexander; Vinnik, Valeria; Kuzmina, Anna; Lezhnev, Nikita; Blokhina, Inna; Shnitenkova, Anastassia; Tuchin, Valery; Rafailov, Edik; Kurths, Jurgen
    There is a hypothesis that augmentation of the drainage and clearing function of the meningeal lymphatic vessels (MLVs) might be a promising therapeutic target for preventing neurological diseases. Here we investigate mechanisms of photobiomodulation (PBM, 1267 nm) of lymphatic drainage and clearance. Our results obtained at optical coherence tomography (OCT) give strong evidence that low PBM doses (5 and 10 J/cm2) stimulate drainage function of the lymphatic vessels via vasodilation (OCT data on the mesenteric lymphatics) and stimulation of lymphatic clearance (OCT data on clearance of gold nanorods from the brain) that was supported by confocal imaging of clearance of FITC-dextran from the cortex via MLVs. We assume that PBM-mediated relaxation of the lymphatic vessels can be possible mechanisms underlying increasing the permeability of the lymphatic endothelium that allows molecules transported by the lymphatic vessels and explain PBM stimulation of lymphatic drainage and clearance. These findings open new strategies for the stimulation of MLVs functions and non-pharmacological therapy of brain diseases.
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    Photostimulation of extravasation of beta-amyloid through the model of blood-brain barrier
    (Basel : MDPI AG, 2020) Zinchenko, Ekaterina; Klimova, Maria; Mamedova, Aysel; Agranovich, Ilana; Blokhina, Inna; Antonova, Tatiana; Terskov, Andrey; Shirokov, Alexander; Navolokin, Nikita; Morgun, Andrey; Osipova, Elena; Boytsova, Elizaveta; Yu, Tingting; Zhu, Dan; Kurths, Juergen; Semyachkina-Glushkovskaya, Oxana
    Alzheimer’s disease (AD) is an incurable pathology associated with progressive decline in memory and cognition. Phototherapy might be a new promising and alternative strategy for the effective treatment of AD, and has been actively discussed over two decades. However, the mechanisms of therapeutic photostimulation (PS) effects on subjects with AD remain poorly understood. The goal of this study was to determine the mechanisms of therapeutic PS effects in beta-amyloid (Aβ)-injected mice. The neurological severity score and the new object recognition tests demonstrate that PS 9 J/cm2 attenuates the memory and neurological deficit in mice with AD. The immunohistochemical assay revealed a decrease in the level of Aβ in the brain and an increase of Aβ in the deep cervical lymph nodes obtained from mice with AD after PS. Using the in vitro model of the blood-brain barrier (BBB), we show a PS-mediated decrease in transendothelial resistance and in the expression of tight junction proteins as well an increase in the BBB permeability to Aβ. These findings suggest that a PS-mediated BBB opening and the activation of the lymphatic clearance of Aβ from the brain might be a crucial mechanism underlying therapeutic effects of PS in mice with AD. These pioneering data open new strategies in the development of non-pharmacological methods for therapy of AD and contribute to a better understanding of the PS effects on the central nervous system. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
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    Photomodulation of lymphatic delivery of liposomes to the brain bypassing the blood-brain barrier: new perspectives for glioma therapy
    (Berlin : de Gruyter, 2021) Semyachkina-Glushkovskaya, Oxana; Fedosov, Ivan; Shirokov, Alexander; Vodovozova, Elena; Alekseeva, Anna; Khorovodov, Alexandr; Blokhina, Inna; Terskov, Andrey; Mamedova, Aysel; Klimova, Maria; Dubrovsky, Alexander; Ageev, Vasily; Agranovich, Ilana; Vinnik, Valeria; Tsven, Anna; Sokolovski, Sergey; Rafailov, Edik; Penzel, Thomas; Kurths, Jürgen
    The blood-brain barrier (BBB) has a significant contribution to the protection of the central nervous system (CNS). However, it also limits the brain drug delivery and thereby complicates the treatment of CNS diseases. The development of safe methods for an effective delivery of medications and nanocarriers to the brain can be a revolutionary step in the overcoming this limitation. Here, we report the unique properties of the lymphatic system to deliver tracers and liposomes to the brain meninges, brain tissues, and glioma in rats. Using a quantum-dot-based 1267 nm laser (for photosensitizer-free generation of singlet oxygen), we clearly demonstrate photostimulation of lymphatic delivery of liposomes to glioma as well as lymphatic clearance of liposomes from the brain. These pilot findings open promising perspectives for photomodulation of lymphatic delivery of drugs and nanocarriers to the brain pathology bypassing the BBB. The lymphatic “smart” delivery of liposomes with antitumor drugs in the new brain tumor branches might be a breakthrough strategy for the therapy of gliomas.