Vol 12, No 5S (2018)

The problem of chronic disorders of consciousness (DOC) remains challenging due to increasing number of these patients and limited therapeutic options. Novel diagnostic approaches provided us with valuable insights into the mechanisms of DOC, such as structural and/or functional disconnection of elements of brain networks that are essential for information processing. Depending on the modality of the study, it may be represented as low-frequency EEG patterns, global or more localized decrease of cortical metabolism on PET scanning, abnormal connectivity structural or functional MRI, or low-differentiated/disintegrated TMSEEG responses. Deeper knowledge of nature of abnormalities underlying chronic DOC may improve accuracy of diagnosis and efficacy of treatment interventions, as well as bring us somewhat closer to the understanding the phenomenon of consciousness.

Non-invasive brain stimulation belongs to most significant neurotechnologies which have arisen in the XXIth century and are characterized by universal medical importance. This group of methods comprises rhythmic transcranial magnetic stimulation (rTMS) and transcranial electric stimulation (transcranial direct current stimulation, tDCS). A spectrum of conditions for which these methods may be effective is steadily expanding and includes a variety of prevalent disorders of the modern society, such as obesity, depression, etc. The low effectiveness of lifestyle modification, as well as a wide range of pharmacological drugs’ side effects and high risks of surgical treatment determine the need to search for new safe methods of correction of eating behavior and obesity, a real pandemy of our society. A number of data suggest the patogenic role of changes of the frontal-striatal interactions in eating behanior disorders. Taking into account the existing models of the development of food dependence, the main approach to the use of rTMS and tDCS is stimulation of areas involved in cognitive control, such as the dorsolateral prefrontal cortex. Current data on studies of rTMS and tDCS in patients with impairment of eating behavior, as well as safety issues of using these techniques in routine clinical practice are reviewed.

The increase in life expectancy is accompanied by an increase in the number of patients suffering from chronic cerebrovascular diseases with progressive cognitive decline, up to dementia. Therefore, the search for new approaches to studying the disease pathogenesis, prevention and treatment is relevant. We analysed the data on correlation of cognitive characteristics with reactions of the autonomic nervous system (ANS) and ANS-regulated systems in normal aging and in patients with vascular encephalopathy (VE). Reactivity of cerebral blood flow as a result of cortical-ANS interaction was studied, characteristics of cerebral blood flow influencing the interhemispheric energetic processes (studied with direct current potentials of the brain) were analyzed, and correlation of blood pressure and heart rate with cognitive characteristics were assessed. Since the signs of cognitive decline are observed during normal aging and VE, an attempt was made to analyze the dependence of cognitive and ANS functions not only on VE, but also on the age. We showed some specific features of cortical-ANS interaction in groups of patients divided in accordance with small criteria of functional asymmetry. The obtained results are of value for studying VE pathogenesis and for prognosing cognitive impairment in patients with VE.

Modern methods of immunohistochemistry and computer morphometry provide powerful possibilities for the study of pathogenetic patterns of neurodegeneration process occurring in physiological aging of men and women, as well as in experimental animals on modeling of Parkinson’s and Huntington's diseases. Threedimensional reconstruction of the substantia nigra pars compacta of the human and rat brains revealed both common features in their organization (heterogeneity of structures) and differences in quantitative morphochemical parameters determining their species-specific characteristics. On modeling of the Huntington's disease with the neurotoxin 3-nitropropionic acid (3-NPA), it was shown not only the death of neurons in the striatum and a decrease in its dopaminergic innervation, but also dysfunction of astrocytes with reduced expression of glutamine synthase that can increase the extracellular content of glutamate. The latter,along with direct succinate dehydrogenase-blocking action of 3-NPA, is one of the factors leading to neurodegenerative changes in the striatum. On modeling of Parkinson's disease, the important role of neuroglia in the neurodegenerative process was shown: it was found that activated astroglia had not only destructive, but also neuroprotective functions, which may serve the basis for the development of respective methods of pharmacological correction directed at regulation of the of glial cell functions.

Cellular models are a very important research tool in modern neurobiology. The presented review of Russian and international literature summarizes the main data of experimental studies, conducted over the past 15 years, aimed at modeling in vitro acute and chronic forms of cerebral pathology in order to reveal the mechanisms of their pathogenesis and to develop approaches to their pharmacological correction. The results of modeling of ischemic neurodestructive processes, epilepsy, Parkinson's disease, Alzheimer's disease and Huntington's disease, obtained using modern cellular research methods, such as cell cultivation in a multielectrode system and technology of induced pluripotent stem cells, are presented. A number of key concepts related to this problem are illustrated with the data obtained by the author and his laboratory. In conclusion, the short-term goals and prospects of in vitro studies of pathogenic mechanisms of neurological diseases and of the search for new neuroprotectors are formulated.

Integrity of neurovascular unit (NVU) and interaction of its components is the basis for brain function. Exceptional role of NVU for providing metabolism of all cerebral processes substantiates obligate participation in pathophysiology of wide range of neurological disorders. Established similarity of structural changes in NVU at early stages of aging and hypertensive cerebral microangiopathy (CMA) suggests common pathogenic mechanisms of its damage and, in view of reversibility of early changes in neurovascular coupling (NVC), allows considering several forms of CMA as variants of early accelerated vascular wall aging. Understanding small vessel damage as a significant risk factor for Alzheimer’s disease and mixed dementias has encouraged revision of the current concept of the development of cognitive decline. A universal role of early NVC impairments in the development of various dementias has been shown. Further studies should improve our understanding of mechanisms of NVC impairment, role of classical and newly specified risk factors in their development and perspectives for preventive strategies. Apparently, success can be achieved through collaboration of neuroscience researchers, which allows translation of advantages of fundamental studies into clinical practice

Monoclonal antibodies are one of the most fastly developing areas of specific therapy for cancer, infectious, autoimmune and demyelinating diseases. The main targets of monoclonal antibodies in autoimmune and demyelinating diseases are T and B-lymphocytes, cytokines, complement, and adhesion molecules. In the field of neurodegenerative diseases, the largest number of studies has been carried out in patients with Alzheimer's disease, in which monoclonal antibodies are targeted to brain aggregates of beta-amyloid. This review presents new therapeutic approaches to the use of antibody fragments, with a focus of their new class, nanobodies. A special attention is paid to new anti-CD20 and anti-CD19 monoclonal antibody drugs in multiple sclerosis (ocrelizumab, ofatumumab) and neuromyelitis optica (inebilizumab). Ocrelizumab is the first medication that proved to be effective in primary progressive multiple sclerosis. There have been significant advances in the treatment of neuromyelitis optica: the first multicenter study of Inebilizumab (MEDI-551) is currently underway.