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160. Photodynamic Opening of the Blood–Brain Barrier Using Different Photosensitizers in Mice.

Author

Semyachkina-Glushkovskaya, Oxana, Borisova, Ekaterina, Mantareva, Vanya, Angelov, Ivan, Eneva, Ivelina, Terskov, Andrey, Mamedova, Aysel, Shirokov, Alexander, Khorovodov, Alexander, Klimova, Maria, Agranovich, Ilana, Blokhina, Inna, Lezhnev, Nikita, and Kurths, Jurgen

Subjects
BLOOD-brain barrier, PHOTOSENSITIZERS, BRAIN diseases, VASCULAR endothelium, GLIOBLASTOMA multiforme, ZINC phthalocyanine
Abstract

In a series of previous studies, we demonstrated that the photodynamic therapy (PDT), as a widely used tool for treatment of glioblastoma multiforme (GBM), also site-specifically opens the blood–brain barrier (BBB) in PDT-dose and age-related manner via reversible disorganization of the tight junction machinery. To develop the effective protocol of PDT-opening of the BBB, here we answer the question of what kind of photosensitizer (PS) is the most effective for the BBB opening. We studied the PDT-opening of the BBB in healthy mice using commercial photosensitizers (PSs) such as 5-aminolevulenic acid (5-ALA), aluminum phthalocyanine disulfonate (AlPcS), zinc phthalocyanine (ZnPc) and new synthetized PSs such as galactose functionalized ZnPc (GalZnPc). The spectrofluorimetric assay of Evans Blue albumin complex (EBAC) leakage and 3-D confocal imaging of FITC-dextran 70 kDa (FITCD) extravasation clearly shows a revisable and dose depended PDT-opening of the BBB to EBAC and FITCD associated with a decrease in presence of tight junction (TJ) in the vascular endothelium. The PDT effects on the BBB permeability, TJ expression and the fluorescent signal from the brain tissues are more pronounced in PDT-GalZnPc vs. PDT-5-ALA/AlPcS/ZnPc. These pre-clinical data are the first important informative platform for an optimization of the PDT protocol in the light of new knowledge about PDT-opening of the BBB for drug brain delivery and for the therapy of brain diseases. [ABSTRACT FROM AUTHOR]

Published
2020
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161. Photodynamic opening of blood-brain barrier

Author

Semyachkina-glushkovskaya, Oxana, Kurths, Jürgen, Borisova, Ekaterina, Sokolovski, Sergei, Mantareva, Vanya, Angelov, Ivan, Shirokov, Alexander, Navolokin, Nikita, Shushunova, Natalia, Khorovodov, Alexander, Ulanova, Maria, Sagatova, Madina, Agranivich, Ilana, Sindeeva, Olga, Gekalyuk, Artem, Bodrova, Anastasiya, Rafailov, Edik, Semyachkina-glushkovskaya, Oxana, Kurths, Jürgen, Borisova, Ekaterina, Sokolovski, Sergei, Mantareva, Vanya, Angelov, Ivan, Shirokov, Alexander, Navolokin, Nikita, Shushunova, Natalia, Khorovodov, Alexander, Ulanova, Maria, Sagatova, Madina, Agranivich, Ilana, Sindeeva, Olga, Gekalyuk, Artem, Bodrova, Anastasiya, and Rafailov, Edik

Abstract

Photodynamic treatment (PDT) causes a significant increase in the permeability of the blood-brain barrier (BBB) in healthy mice. Using different doses of laser radiation (635 nm, 10-40 J/cm2 ) and photosensitizer (5-aminolevulinic acid – 5-ALA, 20 and 80 mg/kg, i.v.), we found that the optimal PDT for the reversible opening of the BBB is 15 J/cm2 and 5- ALA, 20 mg/kg, exhibiting brain tissues recovery 3 days after PDT. Further increases in the laser radiation or 5-ALA doses have no amplifying effect on the BBB permeability, but are associated with severe damage of brain tissues. These results can be an informative platform for further studies of new strategies in brain drug delivery and for better understanding of mechanisms underlying cerebrovascular effects of PDT-related fluorescence guided resection of brain tumor

Published
2017

162. Laser-induced generation of single oxygen: new strategies in treatment of brain tumor

Author

Semyachkina-Glushkovskaya, Oxana, primary, Borisova, Ekaterina, additional, Sokolovski, Sergei, additional, Mantareva, Vanya, additional, Angelov, Ivan, additional, Shirokov, Alexander, additional, Navolokin, Nikita, additional, Shushunova, Natalia, additional, Khorovodov, Alexander, additional, Ulanova, Maria, additional, Sagatova, Madina, additional, Agranivich, Ilana, additional, Bodrova, Anastasiya, additional, Rafailov, Edik, additional, and Tuchin, Valery, additional

Published
2017
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163. The Stress and Vascular Catastrophes in Newborn Rats: Mechanisms Preceding and Accompanying the Brain Hemorrhages

Author

Glushkovskaya, Oxana, Borisova, Ekaterina, Abakumov, Maxim, Gorin, Dmitry, Avramov, Latchezar, Fedosov, Ivan, Namykin, Anton, Abdurashitov, Arkady, Serov, Alexander, Pavlov, Alexey, Zinchenko, Ekaterina, Lychagov, Vlad, Navolokin, Nikita, Shirokov, Alexander, Maslyakova, Galina, Zhu, Dan, Luo, Qingming, Chekhonin , Vladimir P., Tuchin, Valery, Kurths, Jürgen, Glushkovskaya, Oxana, Borisova, Ekaterina, Abakumov, Maxim, Gorin, Dmitry, Avramov, Latchezar, Fedosov, Ivan, Namykin, Anton, Abdurashitov, Arkady, Serov, Alexander, Pavlov, Alexey, Zinchenko, Ekaterina, Lychagov, Vlad, Navolokin, Nikita, Shirokov, Alexander, Maslyakova, Galina, Zhu, Dan, Luo, Qingming, Chekhonin , Vladimir P., Tuchin, Valery, and Kurths, Jürgen

Abstract

In this study, we analyzed the time-depended scenario of stress response cascade preceding and accompanying brain hemorrhages in newborn rats using an interdisciplinary approach based on: a morphological analysis of brain tissues, coherent-domain optical technologies for visualization of the cerebral blood flow, monitoring of the cerebral oxygenation and the deformability of red blood cells (RBCs). Using a model of stress-induced brain hemorrhages (sound stress, 120 dB, 370 Hz), we studied changes in neonatal brain 2, 4, 6, 8 h after stress (the pre-hemorrhage, latent period) and 24 h after stress (the post-hemorrhage period). We found that latent period of brain hemorrhages is accompanied by gradual pathological changes in systemic, metabolic, and cellular levels of stress. The incidence of brain hemorrhages is characterized by a progression of these changes and the irreversible cell death in the brain areas involved in higher mental functions. These processes are realized via a time-depended reduction of cerebral venous blood flow and oxygenation that was accompanied by an increase in RBCs deformability. The significant depletion of the molecular layer of the prefrontal cortex and the pyramidal neurons, which are crucial for associative learning and attention, is developed as a consequence of homeostasis imbalance. Thus, stress-induced processes preceding and accompanying brain hemorrhages in neonatal period contribute to serious injuries of the brain blood circulation, cerebral metabolic activity and structural elements of cognitive function. These results are an informative platform for further studies of mechanisms underlying stress-induced brain hemorrhages during the first days of life that will improve the future generation's health., Peer Reviewed

Published
2016

164. The Stress and Vascular Catastrophes in Newborn Rats: Mechanisms Preceding and Accompanying the Brain Hemorrhages

Author

Semyachkina-Glushkovskaya, Oxana, primary, Borisova, Ekaterina, additional, Abakumov, Maxim, additional, Gorin, Dmitry, additional, Avramov, Latchezar, additional, Fedosov, Ivan, additional, Namykin, Anton, additional, Abdurashitov, Arkady, additional, Serov, Alexander, additional, Pavlov, Alexey, additional, Zinchenko, Ekaterina, additional, Lychagov, Vlad, additional, Navolokin, Nikita, additional, Shirokov, Alexander, additional, Maslyakova, Galina, additional, Zhu, Dan, additional, Luo, Qingming, additional, Chekhonin, Vladimir, additional, Tuchin, Valery, additional, and Kurths, Jürgen, additional

Published
2016
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166. Cerebral venous circulatory disturbance as an informative prognostic marker for neonatal hemorrhagic stroke

Author

Semyachkina-Glushkovskaya, Oxana, additional, Pavlov, Alexey, additional, Navolokin, Nikita, additional, Lychagov, Vladislav, additional, Abdurashitov, Arkady, additional, Zinchenko, Ekaterina, additional, Gekaluk, Artemiy, additional, Zhu, Dan, additional, Shi, Rui, additional, Luo, Qingming, additional, and Tuchin, Valery, additional

Published
2016
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169. Physico-chemical and biochemical approaches to assessing the development of precancerous pathologies of the gastrointestinal tract during their modeling in mice with complex effects of stress factors of different nature

Author

Alieva, Zamira O., additional, Kanevskiy, Matvej V., additional, Galitskaya, Anna A., additional, Mironova, Irina K., additional, Pleshakova, Ekaterina V., additional, Velikov, Vladimir A., additional, Chumakov, Daniil S., additional, Semyachkina-Glushkovskaya, Oxana V., additional, and Konnova, Svetlana A., additional

Published
2016
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174. Optical <italic>in vivo</italic> and <italic>ex vivo</italic> imaging of glioma cells migration via the cerebral vessels: Prospective clinical application of the beta2-adrenoreceptors blockade for glioma treatment.

Author

Pavlova, Olga, Shirokov, Alexander, Fomin, Alexander, Navolokin, Nikita, Terskov, Andrey, Khorovodov, Alexander, Namykin, Anton, Pavlov, Alexey, Tuchin, Valery, and Semyachkina-Glushkovskaya, Oxana

Subjects
GLIOMAS, CANCER, TUMORS, CEREBRAL small vessel diseases, SYMPATHETIC nervous system
Abstract

Malignant gliomas are highly invasive tumors that use the cerebral vessels for invasion due to high vascular fragility of the blood–brain barrier (BBB). On one hand, glioma is characterized by the BBB disruption, on the other hand, drug brain delivery via the BBB is a big challenge in glioma therapy. The limited information about vascular changes associated with glioma growth is a reason of slow progress in prevention of glioma development. Here, we present in vivo and ex vivo study of the BBB disruption and glioma cells (GCs) migration in rats using fluorescence and confocal microscopy. We uncovered a local breach in the BBB in the main tumor mass but not within the border of normal and malignant cells, where the BBB was impermeable for high weight molecules. The migration of GCs were observed via the cerebral vessels with the intact BBB that was associated with macrophages infiltration. The mechanisms underlying glioma progression remain unknown but there is an evidence that the sympathetic nervous system (SNS) via activation of vascular beta2-adrenoreceptors (B2-ADRs) can play an important role in tumor metastasis. Our results clearly show an increase in the expression of vascular B2-ADRs and production of the beta-arrestin-1 — co-factor of B2-ADRs signaling pathway in rats with glioma. Pharmacological blockade of B2-ADRs reduces the BBB disruption, macrophages infiltration, GCs migration and increases survival rate. These data suggest that the blockade of B2-ADRs may be a novel adjuvant therapeutic strategy to reduce glioma progression and prevent metastasis. [ABSTRACT FROM AUTHOR]

Published
2018
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180. Brain Waste Removal System and Sleep: Photobiomodulation as an Innovative Strategy for Night Therapy of Brain Diseases.

Author

Semyachkina-Glushkovskaya, Oxana, Fedosov, Ivan, Penzel, Thomas, Li, Dongyu, Yu, Tingting, Telnova, Valeria, Kaybeleva, Elmira, Saranceva, Elena, Terskov, Andrey, Khorovodov, Alexander, Blokhina, Inna, Kurths, Jürgen, and Zhu, Dan

Subjects
*BRAIN diseases, *ALZHEIMER'S disease, *PHOTOBIOMODULATION therapy, *PARKINSON'S disease, *NEUROREHABILITATION, *FOOD industrial waste
Abstract

Emerging evidence suggests that an important function of the sleeping brain is the removal of wastes and toxins from the central nervous system (CNS) due to the activation of the brain waste removal system (BWRS). The meningeal lymphatic vessels (MLVs) are an important part of the BWRS. A decrease in MLV function is associated with Alzheimer's and Parkinson's diseases, intracranial hemorrhages, brain tumors and trauma. Since the BWRS is activated during sleep, a new idea is now being actively discussed in the scientific community: night stimulation of the BWRS might be an innovative and promising strategy for neurorehabilitation medicine. This review highlights new trends in photobiomodulation of the BWRS/MLVs during deep sleep as a breakthrough technology for the effective removal of wastes and unnecessary compounds from the brain in order to increase the neuroprotection of the CNS as well as to prevent or delay various brain diseases. [ABSTRACT FROM AUTHOR]

Published
2023
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181. Optical monitoring of stress-related changes in the brain tissues and vessels associated with hemorrhagic stroke in newborn rats

Author

Semyachkina-Glushkovskaya, Oxana, primary, Pavlov, Alexey, additional, Kurths, Jürgen, additional, Borisova, Ekaterina, additional, Gisbrecht, Alexander, additional, Sindeeva, Olga, additional, Abdurashitov, Arkady, additional, Shirokov, Alexander, additional, Navolokin, Nikita, additional, Zinchenko, Ekaterina, additional, Gekalyuk, Artem, additional, Ulanova, Maria, additional, Zhu, Dan, additional, Luo, Qingming, additional, and Tuchin, Valery, additional

Published
2015
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186. Blood-brain barrier and cerebral blood flow: Age differences in hemorrhagic stroke

Author

Ulanova Maria, Sindeeva Olga, Semyachkina-Glushkovskaya Oxana, Gekaluk Artem, Zinchenko Ekaterina, Yankovskaya Ludmila, Tuchin Valery, Abdurashitov Arkady, Sindeev Sergey, and M. Kassim

Subjects
Cerebral veins, medicine.medical_specialty, Cerebellum, cerebral blood flow, Biomedical Engineering, Medicine (miscellaneous), age differences, Blood–brain barrier, lcsh:Technology, Internal medicine, Cortex (anatomy), medicine, lcsh:QC350-467, Stroke, brain blood barrier, Neonatal stroke, medicine.diagnostic_test, business.industry, lcsh:T, Magnetic resonance imaging, medicine.disease, Atomic and Molecular Physics, and Optics, Electronic, Optical and Magnetic Materials, medicine.anatomical_structure, Cerebral blood flow, Anesthesia, Cardiology, business, lcsh:Optics. Light
Abstract

Neonatal stroke is similar to the stroke that occurs in adults and produces a significant morbidity and long-term neurologic and cognitive deficits. There are important differences in the factors, clinical events and outcomes associated with the stroke in infants and adults. However, mechanisms underlying age differences in the stroke development remain largely unknown. Therefore, treatment guidelines for neonatal stroke must extrapolate from the adult data that is often not suitable for children. The new information about differences between neonatal and adult stroke is essential for identification of significant areas for future treatment and effective prevention of neonatal stroke. Here, we studied the development of stress-induced hemorrhagic stroke and possible mechanisms underlying these processes in newborn and adult rats. Using histological methods and magnetic resonance imaging, we found age differences in the type of intracranial hemorrhages. Newborn rats demonstrated small superficial bleedings in the cortex while adult rats had more severe deep bleedings in the cerebellum. Using Doppler optical coherent tomography, we found higher stress-reactivity of the sagittal sinus to deleterious effects of stress in newborn vs. adult rats suggesting that the cerebral veins are more vulnerable to negative stress factors in neonatal vs. adult brain in rats. However, adult but not newborn rats demonstrated the stroke-induced breakdown of blood brain barrier (BBB) permeability. The one of possible mechanisms underlying the higher resistance to stress-related stroke injures of cerebral vessels in newborn rats compared with adult animals is the greater expression of two main tight junction proteins of BBB (occludin and claudin-5) in neonatal vs. mature brain in rats.

Published
2015
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187. The stress-related changes in the cerebral blood flow in newborn rats with intracranial hemorrhage: metabolic and endothelial mechanisms

Author

Sindeeva, Olga, primary, Borisova, Ekaterina, additional, Abdurashitov, Arkady, additional, Zhinchenko, Ekaterina, additional, Gekalyuk, Artem, additional, Ulanova, Maria, additional, Sharif, Aly Esmat, additional, Razubaeva, Victoria, additional, Serov, Sergey, additional, Yankovskaya, Ludmila, additional, Tuchin, Valery, additional, and Semyachkina-Glushkovskaya, Oxana, additional

Published
2015
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191. THE EXPERIMENTAL STUDY OF STRESS-RELATED PATHOLOGICAL CHANGES IN CEREBRAL VENOUS BLOOD FLOW IN NEWBORN RATS ASSESSED BY DOCT

Author

SEMYACHKINA-GLUSHKOVSKAYA, OXANA V., primary, LYCHAGOV, VLADISLAV V., additional, BIBIKOVA, OLGA A., additional, SEMYACHKIN-GLUSHKOVSKIY, IGOR A., additional, SINDEEV, SERGEY S., additional, ZINCHENKO, EKATERINA M., additional, KASSIM, MOHHANAD M., additional, ALI, AL-FATLE FATEMA, additional, LEITH, AL HASSANI, additional, ULANOVA, MARIA V., additional, and TUCHIN, VALERY V., additional

Published
2013
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192. Decomposition of Near-Infrared Spectroscopy Signals Using Oblique Subspace Projections: Applications in Brain Hemodynamic Monitoring.

Author

Caicedo, Alexander, Varon, Carolina, Hunyadi, Borbala, Papademetriou, Maria, Tachtsidis, Ilias, Van Huffel, Sabine, Keum-Shik Hong, Chernomordik, Victor, Semyachkina-Glushkovskaya, Oxana, and Meglinski, Igor

Subjects
NEAR infrared reflectance spectroscopy, TIKHONOV regularization, BIOMEDICAL signal processing, HEMODYNAMICS, EXTRACORPOREAL membrane oxygenation, OXYGENATION (Chemistry)
Abstract

Clinical data is comprised by a large number of synchronously collected biomedical signals that are measured at different locations. Deciphering the interrelationships of these signals can yield important information about their dependence providing some useful clinical diagnostic data. For instance, by computing the coupling between Near-Infrared Spectroscopy signals (NIRS) and systemic variables the status of the hemodynamic regulation mechanisms can be assessed. In this paper we introduce an algorithm for the decomposition of NIRS signals into additive components. The algorithm, SIgnal DEcomposition base on Obliques Subspace Projections (SIDE-ObSP), assumes that the measured NIRS signal is a linear combination of the systemic measurements, following the linear regression model y = Ax + ε. SIDE-ObSP decomposes the output such that, each component in the decomposition represents the sole linear influence of one corresponding regressor variable. This decomposition scheme aims at providing a better understanding of the relation between NIRS and systemic variables, and to provide a framework for the clinical interpretation of regression algorithms, thereby, facilitating their introduction into clinical practice. SIDE-ObSP combines oblique subspace projections (ObSP) with the structure of a mean average system in order to define adequate signal subspaces. To guarantee smoothness in the estimated regression parameters, as observed in normal physiological processes, we impose a Tikhonov regularization using a matrix differential operator. We evaluate the performance of SIDEObSP by using a synthetic dataset, and present two case studies in the field of cerebral hemodynamics monitoring using NIRS. In addition, we compare the performance of this method with other system identification techniques. In the first case study data from 20 neonates during the first 3 days of life was used, here SIDE-ObSP decoupled the influence of changes in arterial oxygen saturation from the NIRS measurements, facilitating the use of NIRS as a surrogate measure for cerebral blood flow (CBF). The second case study used data from a 3-years old infant under Extra Corporeal Membrane Oxygenation (ECMO), here SIDE-ObSP decomposed cerebral/peripheral tissue oxygenation, as a sum of the partial contributions from different systemic variables, facilitating the comparison between the effects of each systemic variable on the cerebral/peripheral hemodynamics. [ABSTRACT FROM AUTHOR]

Published
2016
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194. The assessment of pathological changes in cerebral blood flow in hypertensive rats with stress-induced intracranial hemorrhage using Doppler OCT: Particularities of arterial and venous alterations/Die Beurteilung von pathologischen Veränderungen der Hirndurchblutung bei hypertensiven Ratten mit Stress-induzierten intrakraniellen Blutungen mittels Doppler-OCT: Besonderheiten von arteriellen und venösen Veränderungen

Author

Semyachkina-Glushkovskaya, Oxana V., primary, Lychagov, Vladislav V., additional, Bibikova, Olga A., additional, Semyachkin-Glushkovskiy, Igor A., additional, Sindeev, Sergey S., additional, Zinchenko, Ekaterina M., additional, Kassim, Mohhanad M., additional, Braun, Hans A., additional, Al-Fatle, Fatema, additional, Al Hassani, Leith, additional, and Tuchin, Valery V., additional

Published
2013
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199. Physico-chemical and biochemical approaches to assessing the development of precancerous pathologies of the gastrointestinal tract during their modeling in mice with complex effects of stress factors of different nature

Author

Genina, Elina A., Tuchin, Valery V., Derbov, Vladimir L., Postnov, Dmitry E., Meglinski, Igor V., Larin, Kirill V., Pravdin, Alexander B., Alieva, Zamira O., Kanevskiy, Matvej V., Galitskaya, Anna A., Mironova, Irina K., Pleshakova, Ekaterina V., Velikov, Vladimir A., Chumakov, Daniil S., Semyachkina-Glushkovskaya, Oxana V., and Konnova, Svetlana A.

Published
2016
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