Репозиторий Университета

© 2018 IEEE. In our work, we have performed in vitro terahertz (THz) measurements of gelatin-embedded malignant human brain gliomas using the THz pulsed spectroscopy. The gelatin embedding yields sustain the THz response of tissues close to that of the freshly-excised ones for a long time after the resection. We have observed significant differences between the THz responses of normal and pathological tissues of the brain, which highlights a potential of the THz technology in label-free intraoperative neurodiagnosis of tumors.

© 2018 IEEE. Modern progress in terahertz (THz) diagnostics of malignancies, including non-invasive, least-invasive and intraoperative techniques is briefly discussed. Special attention is paid to intraoperative diagnosis of brain tumors, which is a rapidly developing field nowadays. We discuss our recent results in this research field, which are associated with (i) in vitro studies the THz dielectric response of gelatin-embedded human brain tumors (including gliomas and meningiomas featuring different grades), (ii) analysis an ability for differentiation between normal and pathological tissues of the brain relying on the methods of THz spectroscopy and imaging, and, finally, (iii) development of novel THz instrumentation for the intraoperative detection of margins of tumors in order to guarantee its gross total resection.

© 2018 Elsevier B.V. Over the last decade, autophagy has emerged as one of the critical cellular systems that control homeostasis. Besides management of normal homeostatic processes, autophagy can also be induced by tissue damage stress or by rapidly progressing tumors. During tumor progression, autophagy mediates a cellular reaction to the changes inside and outside of cells, which leads to tumor adaptation. Even though the regulation of autophagy seems universal and is a well-described process, its dysregulation and role in glioma progression remain an important topic of investigation. In this review, we summarize recent evidence of autophagy regulation in brain tumor tissues and possible interconnection between signaling pathways that govern cellular responses. This perspective may help to assess the qualitative differences and various outcomes in response to autophagy stimulation.

© 2018 National Academy of Sciences. All rights reserved. Hemispheric asymmetry is a cardinal feature of human brain organization. Altered brain asymmetry has also been linked to some cognitive and neuropsychiatric disorders. Here, the ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) Consortium presents the largest-ever analysis of cerebral cortical asymmetry and its variability across individuals. Cortical thickness and surface area were assessed in MRI scans of 17,141 healthy individuals from 99 datasets worldwide. Results revealed widespread asymmetries at both hemispheric and regional levels, with a generally thicker cortex but smaller surface area in the left hemisphere relative to the right. Regionally, asymmetries of cortical thickness and/or surface area were found in the inferior frontal gyrus, transverse temporal gyrus, parahippocampal gyrus, and entorhinal cortex. These regions are involved in lateralized functions, including language and visuospatial processing. In addition to population-level asymmetries, variability in brain asymmetry was related to sex, age, and intracranial volume. Interestingly, we did not find significant associations between asymmetries and handedness. Finally, with two independent pedigree datasets (n = 1,443 and 1,113, respectively), we found several asymmetries showing significant, replicable heritability. The structural asymmetries identified and their variabilities and heritability provide a reference resource for future studies on the genetic basis of brain asymmetry and altered laterality in cognitive, neurological, and psychiatric disorders.

© 2018, Pleiades Publishing, Inc. The article presents empirical data on the possible use of transcranial Doppler sonography as a method for the identification of functional specialization of hemispheres. We investigated intrahemispheric differences in the increase in blood flow velocity indicators during the performance of cognitive tasks with verbal and nonverbal stimuli in 20 healthy right-handed participants and 20 right-handed patients with local unilateral vascular brain lesions. We observed interhemispheric and intrahemispheric differences in blood flow velocity indicators between arteries during the performance of cognitive tasks with different variants of verbal stimuli in all participants. It has been found that one of the hemispheres plays a dominant role in verbal and nonverbal stimulus processing.

© 2018, Media Sphera Publishing Group. All rights reserved. Objective. To study the effect of сavinton comforte (CC) on the severity of cognitive impairment and motor awkwardness in patients with chronic brain ischemia (HIGM). Material and methods. There were 30 patients (8 men, 22 women) aged 50—65 years (61.6±4.9 years on average) with AHU with cognitive impairment. We used tests of MINI-Cog, Munsterberg, TMT), ADL). QC appointed 10 mg 3 times a day for 3 months. Results. Against the background of therapy, the improvement of constructive praxis and short-term memory, an increase in the speed of visual search and visual-motor function, an increase in the level of selectivity of attention, an improvement in the reproduction of visual images and perception, an increase in the speed of the motor task (drawing strokes). Conclusion. The obtained data can testify about the improvement of indicators of function of a small motility of brushes on the background of improvement of cognitive functions.

© 2018, Media Sphera Publishing Group. All rights reserved. The article addresses gait disturbances in the elderly. It emphasizes that the system that maintains the balance in resting conditions and gait is based on the hierarchical principle and its function depends on the maintenance of integration between vestibular, visual and somatosensory information as well as on cognitive functions. Walking depends on the integrity of frontal-subcortical neuronal circles that support regulatory functions. The main pathogenetic mechanisms of age-related disturbances of balance and gait are a decrease in the efficacy of spinal motorneurons activation caused by Ia-afferentation, a decrease in cortical activation and excitability of corticospinal pathways and in the intensity of intracortical inhibition. The causes of age-related changes in walking are not confined to a single system (e.g., one sensory modality) but have a multisystem character and are involved in many structures. The author analyses the results of recent studies that use functional neuroimaging methods.

© 2018 Media Sphera Publishing Group.All right reserved. Objective. This study aimed to assess the cognitive functions and cerebral blood flow measured with arterial spin labeling (ASL) and their possible correlations with vascular age in untreated middle-aged patients with grade 1-2 essential arterial hypertension (EAH). Methods. We examined 73 subjects aged 40-59 years (33 with EAH and 40 healthy volunteers [controls]). Neuropsychological assessment included Montreal Cognitive Assessment (MoCA), Trail Making test (part A and part B), Stroop Color and Word Test, verbal fluency test (phonemic verbal fluency and semantic verbal fluency), 10-item word list learning task. All subjects underwent brain MRI. MRI protocol included ASL. Vascular age was calculated by two techniques-using Framingham Heart Study risk tables and SCORE project scales. Results. Patients with EAH had lower performance on phonemic verbal fluency test and lower mean MoCA score (29.2±1.4 vs. 28.1±1.7 points) compared to controls (13.4±3.2, p=0.002; 29.2±1.4, p=0.001, respectively). White matter hyperintensities (WMH) were present in 7.5 % controls and in 51.5 % EAH patients (p=0.0002). Cerebral blood flow (CBF) in EAH patients was lower in both right (39.1±5.6 vs. 45.8±3.2 ml/100 g/min) and left frontal lobes of the brain (39.2±6.2 45.2±3.6 ml/100 g/min, respectively) compared to controls (p<0.001). EAH patients without WMH had lower CBF compared to controls (right frontal lobe: 39.5±5.1 ml/100 g/min, p=0.0002; left frontal lobe: 38.9±4.3 ml/100 g/min, p=0.00002). In EAH patients vascular age (57.7±7.4 and 64.6±11.0 years as measured by SCORE project scales and Framingham Heart Study risk tables, respectively) was significantly (p<0.001) greater than chronological one (50.2±6.2 years) and was significantly (p<0.001) higher than the corresponding values in the control group. Correlation analysis revealed negative significant associations between vascular age and MoCA score, phonemic verbal fluency test score and CBF. Conclusions. Treatment-naive middle-aged patients with uncomplicated grade 1-2 EAH compared to normotensive controls have lower mean scores in phonemic fluency test and MoCA, lower CBF, even in the absence of WMH, which correlates with vascular age, particularly with the value calculated by Framingham Heart Study risk tables. Early vascular ageing is important factor of brain impairment in hypertension in middle-aged patients even at early stages of EAH.

© 2018 Ima-Press Publishing House. All Rights Reserved. The recently discovered glymphatic system (GS) ensures the efficient clearance of interstitialfluid and soluble compounds from the central nervous system into cerebrospinal fluid (CSF), which compensates for the lack of conventional lymphatic vessels in the brain parenchyma. This unique anatomical and physiological phenomenon had been unknown until 2012. GS lacks inherent proper vessels P the cuirent of CSF and interstitial fluid is carried out directly inside the arterial walls (the perivascular pathway) or near the walls of the cerebral arteries and veins (the paravascular pathway). Current biorheological technologies could establish a special role of aquaporin-4 in the filtration of CSF and interstitial fluid. The close link between GS and the CSF circulatoiy system allows the established views on fluid dynamics within the brain to be reconsidered. The discoveiy ofGS can contribute to our understanding of the pathogenesis of increased intracranial pressure and neurodegenerative diseases, as well as to the elaboration of new therapeutic approaches to their treatment.

© 2018 Izdatel'stvo Meditsina.All rights reserved. Studied the diagnostic and prognostic significance of N-terminal precursor of natriuretic peptide C-type (NT-proCNP) and brain natriuretic peptide (NT-proBNP) in patients with COPD with pulmonary hypertension (PH). The study included 47 patients with COPD (II-IV degrees of severity, 2016 GOLD, men-44, women-3, mean age 59, 3±9.12 years, disease dura-tion of 13.7±5.93 years, the index of Smoking at 23.1±10, 93 pack-years, BAH of 27.2±12, 06 m!kg2.). Criteria of pulmonary hypertension on the basis of the doppler-echocardiography was an increase ofpulmonary artery systolic pressure (PASP) > 40 mmHg alone. Depending on the presence and degree of enhancement PASP patients were divided into three groups: I-without pulmonary hypertension (PASP < 40 mmHg, n=168), 2-moderate pulmonary hypertension (PASP 40-55 mmHg, n=101), 3-group with severe pulmonary hypertension (PASP > 55 mmHg, n=19). There was a statistically significant intergroup differ-ences (p. 2 0, 001, p J} 0, 001, pl3< 0, 001) values of NT-proCNP and NT-proBNP. There was a significant correlation relation-ship SDLA with the concentration of NT-proCNP (r=0, 53, p<0, 05) and NT-proBNP (r=0, 67; p=0, 05). A high diagnostic value of determination of NT-proCNP and NT-proBNP to predict the development and severity of PH in patients with COPD. Cox regression analysis showed that elevated levels of NT-proCNP and NT-proBNP in COPD patients ofPH c are the predictors of hospital mortality.Grant: The study had no sponsor support.

© 2018, Media Sphera Publishing Group. All rights reserved. Inflammasomes are macromolecular complexes that contain many copies of receptors recognizing molecular patterns of pathogenic agents (PAMP) and damage-associated structures (DAMP), and also include molecules of adapter protein ASC and procaspase- 1. Activation of inflammasomes leads to the formation of active caspase-1 that, in turn, provides the maturation of pro-IL-1β and pro-IL-18 to IL-1β and IL-18. The latter cytokines play an important role in control of neuroinlfammation in the central nervous system contributing to the pathogenesis of a series of neurological, neurodegenerative and mental disorders. The review discusses the involvement of NLRP3 inflammasome and other their types in the development of the traumatic brain injury, ischemic and hemorrhagic stroke, brain tumors, CNS infections, Alzheimer’s and Parkinson’s diseases, epilepsy, amyotrophic lateral sclerosis, depressiver, and consequences of alcohol abuse. The elucidation of molecular mechanisms and signaling pathways controlled by inflammasomes will allow the development of new therapeutic measures for diseases, in which neuroinflammation plays a leading pathogenetic role.

© 2018 Izdatel'stvo Meditsina. All Rights Reserved. In the review article are considered the recent data that emphasize the role of cortical disturbances in the pathogenesis of vestibular disorders. The vestibular system not only provides a link between motor and sensory processes, its functions are much more extensive. The experiments conducted in recent years on primates, as well as the data obtained by neuroimaging methods, have significantly advanced our understanding of the functioning of the vestibular system, especially its central parts. The vestibular cortex can be considered as a network of connections between all cortical areas receiving sensory input from the vestibular system, including cerebral zones in which vestibular information affects the analysis of other sensory (i.e. somatosensory and visual) and motor activity. The pathogenesis of vertigo and tinnitus is especially analyzed.

Copyright © 2018 Institute of Computer Science. The paper proposes a mathematical model for the therapy of glioma, taking into account the blood-brain barrier, radiotherapy and antibody therapy. The parameters were estimated from experimental data and the evaluation of the effect of parameter values on the effectiveness of treatment and the prognosis of the disease were obtained. The possible variants of sequential use of radiotherapy and the effect of antibodies have been explored. The combined use of radiotherapy with intravenous administration of mab Cx43 leads to a potentiation of the therapeutic effect in glioma. Radiotherapy must precede chemotherapy, as radio exposure reduces the barrier function of endothelial cells. Endothelial cells of the brain vessels fit tightly to each other. Between their walls are formed so-called tight contacts, whose role in the provision of BBB is that they prevent the penetration into the brain tissue of various undesirable substances from the bloodstream. Dense contacts between endothelial cells block the intercellular passive transport. The mathematical model consists of a continuous part and a discrete one. Experimental data on the volume of glioma show the following interesting dynamics: after cessation of radio exposure, tumor growth does not resume immediately, but there is some time interval during which glioma does not grow. Glioma cells are divided into two groups. The first group is living cells that divide as fast as possible. The second group is cells affected by radiation. As a measure of the health of the blood-brain barrier system, the ratios of the number of BBB cells at the current moment to the number of cells at rest, that is, on average healthy state, are chosen. The continuous part of the model includes a description of the division of both types of glioma cells, the recovery of BBB cells, and the dynamics of the drug. Reducing the number of well-functioning BBB cells facilitates the penetration of the drug to brain cells, that is, enhances the action of the drug. At the same time, the rate of division of glioma cells does not increase, since it is limited not by the deficiency of nutrients available to cells, but by the internal mechanisms of the cell. The discrete part of the mathematical model includes the operator of radio interaction, which is applied to the indicator of BBB and to glial cells. Within the framework of the mathematical model of treatment of a cancer tumor (glioma), the problem of optimal control with phase constraints is solved. The patient's condition is described by two variables: the volume of the tumor and the condition of the BBB. The phase constraints delineate a certain area in the space of these indicators, which we call the survival area. Our task is to find such treatment strategies that minimize the time of treatment, maximize the patient's rest time, and at the same time allow state indicators not to exceed the permitted limits. Since the task of survival is to maximize the patient's lifespan, it is precisely such treatment strategies that return the indicators to their original position (and we see periodic trajectories on the graphs). Periodic trajectories indicate that the deadly disease is translated into a chronic one.

© 2018 Ima-Press Publishing House. All Rights Reserved. Up to 15% of patients with secondary brain tumors of unknown primary are admitted to a neurosurgery department. Identification of a primary tumor site on the basis of surgical material immunophenotyping in routine clinical practice has a significant potential; however, this requires systematization. Objective: to detect the primary focus of brain carcinoma. Patients and methods: Surgical specimens from 7 patients with brain tumor of unknown primary were investigated using light optical microscopy and an immunohistochemical (IHC) panel including EMA, CK AE1/3, CK7, CK5/6, GFAP, S-100, Vimentin, p63, TTF-1, Uroplakin III (UPIII), CDX2, and Her2/neu. Results and discussion: A study using the IHC panel made it possible to obtain the following tumor phenotypes in the patients: CK5/6+, p63+, CK7+, UPIII+ (urothelial cancer) (n=3); CK5/6-, CK7+, TTF-1+, CDX2- (lung adenocarcinoma) (n=2); CK5/6+, p63+, CK7-, UPIII, TTF-1- (squamous cell carcinoma) (n=1), and CK5/6-, CK7+, TTF-1-, CDX2-, Her2/neu+ (breast cancer) (n=1). Evidence of the primary focus of the tumors was subsequently confirmed by instrumental techniques in all cases when cancer of the breast, lung and urinary system was directly sought. The findings were used to elaborate an algorithm for the differential diagnostic immunophenotyping of brain metastases. Conclusion: The primary focus of brain carcinoma was detected in all cases on the proposed IHC panel. The systematized algorithm for differential diagnostic immunophenotyping can be used in clinical practice.

© 2018, Media Sphera Publishing Group. All rights reserved. The well apparent signs of the proliferative reaction and activity of the nucleolus organizer in astrocytes within the zone of injury and at its periphery are considered to be the indicators of the participation of these cells in all the phases of the inflammatory and reparative processes associated with the brain injury. The objective of the present study was the evaluation of the changes in the number of the nucleoli in the nuclei of astrocytes during the acute post-traumatic period following the craniocerebral injury. A total of 26 cases of death of the men and women at the age from 36 to 50 years caused by the craniocerebral trauma were available for the examination. The tissue samples were stained with hematoxylin and eosin, based on the use of the Perls’ Prussian blue staining protocol or by means of the AgNOR staining technique. The astrocytes in the regions immediately adjacent to the sites of brain injury were shown to undergo areactive necrosis during the first hours after the damage had been inflicted. The evaluation of the changes in the astrocytes required taking into consideration the influence of autolysis on the character of the signs being identified. The increase of the number of points in the astrocytes in which RNA replication occurs within days 2—4 after the injury can be accounted for by the accumulation of the granules containing silver in the cell nuclei. The cross reactions between hemosiderin and RNA await further investigations. It is concluded that the methods employed in this study may be of diagnostic significance for the purposes of forensic medical histology if used in the combination with other specialized techniques for determining the prescription of the craniocerebral injuries. The combination of the morphological and functional studies opens up the promising prospects for the investigations into the necrotic and proliferative processes in astrocytes associated with brain injuries of different origin.

© 2018 Izdatel'stvo Meditsina. All rights reserved. The cerebrovascular effects of 5-hydroxyadamantane-2-one (100 mg/kg, i.v.), nimodipine (0.03 mg/kg, i.v.), and S-amlodi- pine nicotinate (0.1 rag/kg, i.v.) were compared and found to differ significantly. While G ABA-ergic 5-hydroxyadaman- tan-2-one and slow calcium channels blocker nimodipine cause a pronounced increase in cerebral blood supply under conditions of global transient ischemia of the brain, their activity in modeling hemorrhagic stroke is significantly lower. At the same time, S-amlodipine nicotinate equally improves cerebral circulation in both hemorrhagic and ischemic brain damage, i.e., the cerebrovascular effect of S-amlodipine nicotinate in the hemorrhagic stroke model is superior to that of nimodipine and 5-hydroxyadamantan-2-one. This is due to a distinguishing feature of the of S-amlodipine nicotinate action, which, in contrast to 5-hydroxyadamantan-2-one and nimodipine, has a binary vasodilating effect on cerebral vessels: (i) blocking slow calcium channels and (ii) stimulating GABAA-receptors.

© 2018 Ima-Press Publishing House. All rights reservbed. Diffusion tensor magnetic resonance imaging (DT-MRI) is the only noninvasive technique that makes it possible to study white matter microstructure in vivo and to quantify the images obtained. Objective: to study white matter in middle-aged treatment-naïve patients with uncomplicated grade 1-2 essential hypertension (EH), by using DT-MRI. Patients and methods. The investigation enrolled 82 people aged 40-59 years (41 patients with EH and 41 healthy individuals (a control group)). Twenty-four blood pressure monitoring and brain MRI were performed in different modes (T1 MPRAGE, T2 TSE, T2 FLAIR, and DTI). Results. White matter hyperintensities (WMHs) were found in 7.3% of the healthy individuals and in 53.7% of the hypertensive patients (p=0.0002). The latter had significantly lower fractional anisotropy (FA) values in the white matter of the left inferior frontal gyrus than the healthy individuals (0.39±0.06 and 0.45±0.09, respectively; p< 0.001). FA was lower in the hypertensive patients than in the healthy individuals not only in the presence of WMHs (the left inferior frontal gyrus white matter was 0.397±0.071 and 0.45±0.09, respectively; p=0.009; the genu of the corpus callosum was 0.79±0.04 and 0.81±0.05, respectively; p=0.045), but also in the absence of WMHs (the left inferior frontal gyrus white matter was 0.378±0.073 and 0.45±0.09, respectively; p=0.0007). Discussion. The treatment-naïve patients with uncomplicated grade 1-2 EH with short-term (2,3 year) duration were found to have significantly lower FA values in the left inferior frontal gyrus white matter than the healthy normotensive subjects of the same age. Thus, the microstructural integrity of white matter is impaired in middle-aged hypertensive patients even at the earliest disease stages. Conclusion. Middle-aged treatment-naive patients with uncomplicated grade 1-2 EH have lower FA in the left inferior frontal gyrus white matter even in the absence of WMHs.

© 2018 Media Sphera Publishing Group. All rights reserved. The review considers modern ideas about the clinic and pathogenesis of minimal hepatic encephalopathy (MHE). It is discussed the present of cognitive impairment in this category of patients. The data of functional MRI are analyzed, and these results allow taking a fresh look at the origin of clinical disorders in this condition. The importance of cerebral connections disruption is emphasized. It is focused on the fact that in the functioning of the central nervous system the spontaneous activity of the brain has a significant importance. Separately is analyzed "the resting state". It is concluded that MHE, despite its minimal manifestations, is a clinically significant condition requiring attention of a specialists. With that, it is often not diagnosed on time in clinical practice, which could lead to more severe damage of the cerebral functions. As evidenced by the data obtained at the present time, quite extensive changes in the neuronal activity are underlid of the cognitive deficit.

© 2018 Istituto Superiore di Sanita. All Rights Reserved. Parkinson disease is one of the common age-related motor neurodegenerative diseases, in which dopamine neurons degeneration is considered to be pathognomic for the development of motor disfunction. Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family, which is considered to be a key regulator of neuronal plasticity. BDNF, being a large molecule, does not pass through the blood-brain barrier (BBB). Synthetic polymer nanoparticles (NP), covered by surfactant, provide the phenomenon of “Trojan hoarse” and enable BDNF to penetrate into the brain tissue. For modelling of parkinsonism we used an intraperitoneal (i.p.) injection of neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) which was injected to the C57BL/6 mice with subsequest treatment with normal saline (group 1), BDNF (group 2), nanoparticulate BDNF (group 3) and surfactant-coated nanoparticulate BDNF (group 4). After 90 min, 24 hours, 72 hours and 7 days manifestations of parkinsonism were evaluated using behavioural tests of open field, rota-rod, assessment of the tremor, length of the body and pace. At the end of experiment the brain was sampled for histological evaluation of changes in the striatum and midbrain and concentration of BDNF in the brain tissues. The results of the experiments demonstrated that nanoparticulate BDNF covered with surfactant significanltly reduced rigidity of the skeletal muscles, oligokinesia and tremor, and also significantly increased BDNF concentration in the brain tissues.

© 2018, Pediatria Ltd.. All rights reserved.  Objective of the research – to reveal the correlation between neurochemical criteria in the neonatal period and the consequences of severe hypoxic hemorrhagic CNS lesions in children according to catamnesis data. Materials and methods: researchers analyzed 54 cases of newborns of different gestational age (GA) that were in the ICU after birth due to severe condition; all newborns had combined hypoxic hemorrhagic brain lesion detected by neurosonography – periventricular leukomalacia (PVL) and intraventricular hemorrhage (IVH) of various severity. Catamnesis follow-up was performed up to 2–2,5 years of age. The control group consisted of 20 newborns, comparable in GA, body weight at birth, with an Apgar score of at least 6 points in the 1st minute of life and without changes in neurosonography. In the neonatal period, serum concentrations of S100, BDNF, VEGF, ALCAM, DR5 were studied in dynamics using the quantitative ELISA (Enzyme Linked Immuno Sorbent Assay) according to a standard protocol. Results: the concentration of factors contributing to destructive changes in tissues (S100, DR5, ALCAM) in the serum, was in inverse correlation with the level of VEGF and BDNF. The latter had a direct correlation relationship. VEGF directly correlated with CNTF by the end of the 2 nd week of life. Results of catamnesis follow-up: 43 children diagnosed with cerebral palsy, 25 with spastic diplegia, 18 with spastic tetraparesis, and 11 without evident motor disorders. In 28 children I–III level of motor disorders was determined according to GMFS, in 26 children – IV–V level. At the age of 2 years, all children underwent MRI of the brain and gliio-atrophic changes were detected. Significant differences in the implementation of neurological consequences were found between the number of children with grade I and II IVH and PVL and III–IV degree IVH and PVL. Conclusion: children with PVL and IVH III–IV degree have a high risk of severe neurological outcomes – spastic tetraparesis, impaired motor activity by GMFS IV–V level, mental retardation and symptomatic epilepsy.