Background: achievements in neuroscience indicate a signiflicant contribution of inflammation to the pathogenesis of chronic non-communicable diseases of the brain.

The aim of the review was to consider the results of current studies of inflammation activation mechanisms, which realize in infectious and non-infectious pathologies.

Materials and method: Using the keywords “inflammation”, “neuroinflammation”, “chronic diseases”, “inflammatory markers” a search was made for scientific publications in domestic and international databases from the beginning of the 21st century.

Conclusion: the results of the studies made it possible to reveal the universal mechanism of inflammation activation by infectious and non-infectious “sterile” agents (protein aggregates, destruction products of the body’s own tissues, prolonged stress). This not only fundamentally changed the view on the pathogenesis of chronic brain diseases, but also on their early diagnosis, prevention and therapy.

Background: neurodegenerative processes are prognostically dramatic conditions. They are actively studied by both neurologists and psychiatrists. Nosological forms are diverse and include regressive autism, dementia, multiple sclerosis, Parkinson’s disease, Alzheimer’s disease, progressive epilepsy of infancy and childhood, generalized hyperkinesis, Tourette’s syndrome and many other conditions that are common to progressive neurological deficit, loss of cognitive functions, the appearance of nonspecific symptoms of brain irritation (epileptic seizures, hyperkinesis, dystonic states, stereotypes, psychotic episodes and other symptoms). Despite many ongoing studies the treatment of the described conditions is limited to temporary, incomplete and pharmacologically dependent relief of symptoms, since the problem of the etiopathogenesis of these conditions remains open. 
The aim of review is to present current immunological concepts of pathogenesis of neurodegenerative diseases. 
Material and method: using keywords “neuroinflammation, neurodegeneration, multiple sclerosis, Parkinson disease, epilepsy, parasitosis, microbiota” selected relevant scientific publications in domestic and international databases. 
Conclusion: recent advances in neuroimmunology show a significant role of neuroinflammation in the triggering and development of neurodegenerative processes, some of which are autoimmune in nature, which is confirmed by the indicators of immunity intensity introduced into clinical practice and by the detected antibody titers to brain tissues. In recent decades in a series of scientific works attention has been paid to the study of infectious agents detected in the immunological screening of patients with neurodegeneration, however, these data are fragmented and contradictory, and therefore are ignored by the medical community. This review presents a modern view of the etiopathogenesis of neurodegenerative diseases from the point of view of the summative antigenic burden, assessment of the immunological potential, homeostatic resource, and compensatory capabilities of the human body, which as a result can become a starting point for proposing new therapeutic strategies for the treatment of these intractable diseases. 

Background: schizophrenia is associated with neuroinflammation and dysregulation of the immune system involving microglia. The study of microglial reactivity in schizophrenia is at an early stage. The results of neuroimaging and postmortem studies are contradictory. 
Aim of the study: to analyze and summarize the results of morphometric studies of the microglial reactivity at the ultrastructural level in postmortem prefrontal cortex in schizophrenia compared to healthy controls. 
Material and methods: the study was performed in layer 5 of the prefrontal cortex in 21 cases of schizophrenia and 20 control cases using transmission electron microscopy and morphometry. 
Results and conclusion: we found that chronic schizophrenia is characterized by a combination of signs of activation, progressive dystrophy and accelerated aging of microglia. The reactivity of microglia in schizophrenia is associated with age, the age of onset of the disease, the duration of the disease and the type of course of the disease, which indicates the participation of microglia in the pathological process in schizophrenia. Damage and deficit mitochondria and the disturbance of energy metabolism can play a key role in microglial dysfunction in schizophrenia.

Background: Immunological and genetic studies of schizophrenia form two areas of biological psychiatry in which significant progress has been made in recent years related to understanding the role of both neuroinflammation and genetic vulnerability in the development of this disease. However, data to explain the complicity of these two factors in the etiology and pathogenesis of schizophrenia are still insufficient. 
The aim of the review is to assess the degree of interaction between genetic predisposition and neuroinflammation in the pathogenetic mechanisms of schizophrenia based on the currently available information on genes associated with the immune system according to genome-wide association analysis (GWAS), as well as models that involve the interaction of immunological and genetic factors, including taking into account environmental adversities. 
Material and method: using keywords “genome-wide association study, Mendelian randomization, regulatory regions, maternal immunity activation, synaptic pruning, microglia” both in international and domestic databases the scientific publications selected. 
Conclusions: recent studies have identified genomic regions that contain genes involved in the functioning of the immune system. Particular attention is paid to the MHC region, and one of the most important achievements in its study is the establishment of the role of the complement gene (component C4A) in the formation of synapses and their abnormal elimination. Other genes, both inside and outside the major histocompatibility complex (MHC) region, are of interest, and their functions in the brain and their involvement in the pathogenesis of schizophrenia have yet to be elucidated. The establishment of causal relationships between GWAS data for schizophrenia and immunological indicators of inflammation using the Mendelian randomization (MR method) indicates that the increase in the level of pro-inflammatory cytokines in patients with schizophrenia is an intrinsic symptom of the disease, and is not a consequence of the course of the pathological process. Adverse environmental factors play an important role in the interaction of genetic variants associated with schizophrenia and microglial activation, which leads to synaptic disorders.

Background: the prevalence of autism spectrum disorders (ASD) is increasing every year, however, diagnostic and therapeutic options are still limited. 
Aim: identification the patterns of the neuroinflammation process in the etiopathogenesis of ASD of child patients. 
Patients and methods: clinical, anamnestic and laboratory data of 85 child patients with a confirmed ASD diagnosis. Each patient was assessed for the level of neurospecific proteins (neuron-specific enolase (NSE), S100b protein), the indices of the “Neuro-immuno-test” panel (leukocyte elastase (LE) and α1-proteinase inhibitor (α1-PI) activity, autoantibodies to S100b protein and myelin basic protein) in the blood before and after a standardized three-month-course of treatment. The reference interval of the laboratory was taken as normal values. The clinical picture was assessed according to the Childhood Autism Rating Scale (CARS). The correlation calculations were carried out in the MS Excel program. 
Results: in this work we describe the dynamics of the neuroinflammation process parameters in children with autism-like syndrome and psycho-speech development delay on the basis of complex anti-inflammatory therapy. The results of the research prove the increase in NSE and S100b protein quantity among 85% of patients before the treatment. More than 60% of patients had the increase of the parameters of the Neuro-test panel. The severity levels of symptoms among patients according to the scales used specified moderate and severe autism. The quantity of neurospecific proteins and immunological parameters correlated with CARS scale scores. Positive dynamics of clinical symptoms and studied parameters decrease were observed while therapy. The use of the parameters allows to evaluate objectively the severity levels of the patient’s immunomitochondrial status and shows a congruent change on the basis of etiopathogenetic therapy.

Background: despite the large number of newly emerging antiepileptic drugs, the frequency of treatment-resistant forms of epilepsy has not decreased, averaging 25–30%. Moreover the number of epileptic encephalopathies of early childhood has increased. One of the reasons of drug resistance is neuroinflammation. 
Aim: to evaluate the role of neuroinflammation in the pathogenesis of severe forms of childhood epilepsy and resistant adult epilepsy.
Patients and methods: the main group 1 — 94 pediatric patients with epileptic encephalopathies, average age 20.4 ± 6.2 months. The control group 1 — 42 pediatric patients in remission of epilepsy, average age 21.3 ± 5.7 months. The main group 2 — 35 adult patients with resistant forms of epilepsy, average age 38.3 ± 7.9 years. The control group 2 — adult patients in remission of epilepsy 47 patients, average age 34.2 ± 8.6 years. The following blood levels were analyzed: neuron-specific enolase, S100 protein, eosinophilic cationic protein, IgE total level, total level of circulating immune complexes, leukocyte elastase and alpha-1 antitrypsin. 
Results: in the group of children with epileptic encephalopathies, an increase in neuroinflammation indicators was revealed in most patients. The average level of neuron-specific enolase is 27.6 ± 5.3 ng/ml compared to 14.2 ± 3.5 ng/ml in the control group. The average S100 protein level is 0.232 ± 0.041 ng/ml compared to 0.092 ± 0.024 ng/ml in the control group. The average level of eosinophilic cationic protein is 39.7 ± 9.4 ng/ml compared with 18.2 ± 5.3 ng/ml in the control group. The average IgE level is 157.3 ± 64.2 IU/ml compared to 42.2 ± 17.5 IU/ml in the control group. The average level of circulating immune complexes is 265.6 ± 54.4 UE/ml compared to 56.8 ± 16.8 UE/ml in the control group. In the group of adult patients with resistant forms of epilepsy, an increase in neuroinflammation indicators was revealed in most patients. The average level of neuron-specific enolase is 19.2 ± 7.2 ng/ml compared to 13.1 ± 4.1 ng/ml in the control group. The average S100 protein level is 0.115 ± 0.037 ng/ml compared to 0.093 ± 0.018 ng/ml in the control group. The average level of eosinophilic cationic protein is 24.2 ± 6.7 ng/ml compared to 18.8 ± 4.7 ng/ml in the control group. The average level of total IgE is 117.9 ± 32.6 IU/ml compared to 53.4 ± 18.2 IU/ml in the control group. The average level of circulating immune complexes is 235.2 ± 43.7 UE/ml compared to 62.6 ± 20.4 UE/ml in the control group. The level of leukocyte elastase was increased in 32 (91.4%) patients, the average level was 267.2 ± 36.8 nmol/min × ml compared with 175.2 ± 23.8 nmol/min × ml in the control group. The level of alpha-1 antitrypsin was increased in 33 (94.3%) patients, the average level was 55.2 ± 12.1 ng/ml compared with 26.4 ± 15.6 ng/ml in the control group. 
Conclusion: neuroinflammation is the factor of the development of severe forms of epilepsy and the formation of resistance in epileptic encephalopathies. Epileptic encephalopathies of early childhood according to their etiopathogenesis should be considered as subacute encephalitis, where seizures are only one sign of the pathological inflammatory process. The main clinical aim of the treatment of epileptic encephalopathies is the diagnosis of cumulative antigenic load and the selection of anti-inflammatory therapy.

Background: the results of studying the role of neuroinflammation in the pathogenesis of chronic mental disorders guide the scientific search for ways to apply conceptual notions to clinical practice. 
The aim: to present an overview of clinical and biological studies conducted jointly by clinicians and employees of the Laboratory of Neuroimmunology of the FSBSI “Mental Health Research Centre” and aimed at determination of the significance of immune biomarkers for the diagnosis, prognosis and treatment of various types of mental pathology. 
Method: the methodological equipment of this study is provided by the use of the original “Neuro-immuno-test” medical technology, developed at the FSBSI “Mental Health Researh Centre”, in comparison with the clinical data. 
Results and discussion: summarizing the results of many years of research showed that various inflammatory markers, determined in the blood of patients, can be used to assess the level of inflammation in the brain. Studies in various groups of patients showed that the level of these markers reflected the severity and acuteness of the pathological process in the brain and correlated with the characteristics of the clinical symptoms of patients. The most significant for an objective assessment of the clinical status of patients and the prognosis of the course of the disease are not individual inflammatory markers, but their combinations and ratios. It was found that the quantitative change in immunological parameters was ahead of the change in clinical indicators, confirming their prognostic significance. Elevated blood markers at the stages of the disease, preceding the development of pronounced clinical symptoms, can serve as an objective criterion for the presence of a current pathological process in the brain of patients with a high risk of manifestation of endogenous psychosis. The conducted immunological studies using the “Neuro-Immuno-Test” technology revealed different activation of the immune system in patients with cognitive impairment of varying severity, i.e. from mild cognitive impairment to dementia in Alzheimer's disease (AD). 
Conclusion: differences in immunophenotypes, which have certain quantitative and qualitative features of the spectrum of inflammatory and autoimmune markers, found using the “Neuro-Immuno-Test”, are extremely important both for diagnosis and prognosis, and for therapy optimization.

Background: the etiology and pathogenesis of childhood autism (CA) is one of the important unresolved problems of child psychiatry. It has been shown that the concentration of extracellular DNA (cfDNA) in the blood significantly increases in children with CA, and to the greatest extent in patients with severe CA. Patients with more severe CA also have significantly elevated levels of the oxidized DNA marker 8-OHdG in cfDNA and nuclear DNA samples and the double-strand break marker γH2AX. 
The aim was to study the effect of oxidized cfDNA fragments on the formation of free radicals, oxidation and breaks of nuclear DNA in the peripheral blood mononuclear cells in vitro in children with CA. 
Patients and methods: the study involved 13 patients diagnosed with F84.02 according to ICD-10 and 10 conditionally healthy children as a control group. Clinical-psychopathological, molecularbiological, statistical methods were used. 
Results: oxidized model DNA fragments affect the peripheral blood mononuclear cells of children with CA and conditionally healthy donors in different ways. In the mononuclear cells of conditionally healthy donors, in response to exposure to oxidized DNA fragments, the levels of ROS (reactive oxygen species) (p < 0.05), DNA oxidation (p < 0.05) and chromosome damage (p < 0.05) increase, but within the next 24 hours these indicators return to the previous level. At the same time, in the mononuclear cells of children with CA, the levels of ROS, DNA oxidation, and chromosome damage also increase, but the subsequent decrease occurs more slowly, and the levels of these indicators do not return to their previous values. 
Conclusion: on the basis of the obtained results, it is possible to put forward a hypothesis about the participation of fragments of oxidized extracellular DNA in the pathogenesis of CA.

Background: there is a two-way relationship between the gut microbiota (GM) and the brain, both in normal and pathological conditions. It has been suggested that disturbances in GM composition and function can lead to the activation of (neuro) inflammation or its maintenance in mental disorders. 
Objective: analysis of scientific publications, including the results of our own research on the gut microbiota, its role in the modulation of brain functions and involvement in the maintenance of (neuro)inflammation in endogenous mental disorders. 
Material and method: using the keywords “gut–microbiota” and “microbiota–gut–brain axis/mental disorders”, “inflammation”, “neuroinflammation”, articles and reviews were searched in databases and electronic libraries of scientific publications Medline/PubMed, Scopus, Google Scholar, RSCI, and other sources. 
Results: on the basis of the analysis of literature sources, general information about GM, its composition, functions and main ways of interaction with the brain is given. The role of GM in the development and maintenance of (neuro)inflammation, currently considered as one of the pathogenetic mechanisms of mental disorders, is discussed. Particular attention is paid to the results of own studies on the role of endotoxin (ET) (lipopolysaccharide — LPS) and inflammation in the development of endogenous psychoses and the relationship of these indicators with the effectiveness of pharmacotherapy. 
Conclusion: it has been established that GM is an important participant and regulator of neuro-immune interactions. The possible role of GM in the maintenance of (neuro)inflammation in endogenous mental disorders and the participation of endotoxin aggression (EA) in the formation of therapeutic resistance in endogenous psychoses were revealed.