OBJECTIVE:To study the effect of the new coronavirus infection COVID-19 on the course and prognosis of tuberculous meningoencephalitis in HIV-infected patients. MATERIAL AND METHODS:The main group included 46 patients with human immunodeficiency virus (HIV) and tuberculous meningoencephalitis who were infected with a new coronavirus infection. The comparison group included 52 patients with tuberculous meningoencephalitis and HIV who had no history of the new coronavirus infection. All patients underwent laboratory tests for infectious diseases (including analysis of cerebrospinal fluid (CSF)), parameters of the hemostasis system, CT of the lungs and brain as part of an inpatient examination. RESULTS:The analysis of the obtained data showed that coronavirus infection aggravates the course of tuberculous meningoencephalitis, increases mortality, affects the mechanisms of thanatogenesis, significantly increasing the frequency of multi-organ failure compared to the comparison group. In patients with coronavirus infection, according to the results of computed tomography of the brain, hydrocephalus was recorded more often, mycobacterium DNA was reliably detected in the CSF using polymerase chain reaction, the syndrome of impaired consciousness at presentation was more common, the period from admission to death was significantly reduced. CONCLUSION:New data were obtained, suggesting correlations between the combination of manifestations of tuberculous meningoencephalitis, HIV, and coronavirus infection with acute toxic-infectious encephalopathy syndrome, as well as the role of DIC syndrome, which is common in this category of patients.

In response to ischemic stroke (IS) a natural activation of the stress-realizing system occurs. The features of this activation influence the outcome of the acute period and the prognosis of recovery and can be adjusted. At the same time, the role of the stress-realizing system in the pathogenesis of IS is still unexplored.Objective: to investigate the effect of peripheral blood cortisol concentration on the regulation of apoptosis of neurons of the cerebral cortex in the acute phase of IS.Material and methods. A prospective clinical and pathological study was performed. It included 9 patients with IS in the left middle cerebral artery territory who were admitted to hospital and died in the hyperacute phase of IS and had no infectious complications, allergic reactions or oncological diseases and who did not undergo thrombolysis. The cerebral cortex was examined. Neuron-specific enolase (NSE), protein 53 (p53), caspase 3, caspase 8, Fas receptor (CD95), and Fas apoptotic inhibitory molecule 2 (FAIM2) were determined on the slices using an indirect immunoperoxidase immunohistochemical staining method. A total of 567 microscopic fields were analysed for the group of patients with IS and 63 fields for the control group (three people). Before death, the blood concentrations of sFas, sFasL, cortisol, adrenocorticotropic hormone, adrenaline and norepinephrine were determined by enzyme immunoassay (the control group consisted of 28 people).Results. Significant correlation was found between the proportion of casp3-positive neurons and the concentration of cortisol in peripheral blood in zones 2 (r=0.263; p<0.01) and 3 (r=0.383; p<0.01). In the 2nd zone, significant negative correlation was found with the concentrations of sFas (r=-0.177; p<0.05) and sFasL (r=-0.164; p<0.05); in the 3rd zone, significant positive correlation was found with the ratio of the concentrations of sFasL and sFas (r=0.240; p<0.01). The proportion of Fas-positive neurons in the cerebral cortex correlated significantly with the concentration of the soluble form of this molecule (for the 1st zone – r=0.222, for the 2nd zone – r=0.438, for the 3rd zone – r=0.289; p<0.01) and the ratio of the concentrations of sFasL and sFas (respectively: r=0.231, r=0.266 and r=0.281; p<0.01) in the peripheral blood.Conclusion. Peripheral blood cortisol concentration is a factor that determines the regulation of apoptosis of neurons in the cerebral cortex in the acute phase of IS.

Despite the fact that more than 90 % of tryptophan is metabolized via the kynurenine pathway, the serotonin pathway is of great importance for the functioning of the central nervous system. The main products of this pathway are serotonin and melatonin. They provide maintenance of the sleep-wake mode, modulation of oxidative stress activity, apoptosis of neurons and glial elements, regeneration and neuroinflammation. In the pathogenesis of Alzheimer's disease, neuroinflammation plays one of the main roles. Melatonin and serotonin, being modulators of its intensity, as well as an important component of neurochemical interactions that provide cognitive functions, can be considered as targets for preventive and therapeutic effects.

The article reports on the rarest case of Guillain-Barré syndrome in the form of acute motor-sensory polyneuropathy in a female patient with tuberculous meningitis, disseminated pulmonary tuberculosis, and tuberculous pleurisy. In the neurological status at the exit from the coma, the patient was diagnosed with tetraplegia, bulbar syndrome, and respiratory disorders. Further, within a week, pronounced muscle atrophy appeared. Active etiotropic, pathogenetic therapy, including plasmapheresis, gave a dramatic effect with a significant improvement in the condition and a gradual regression of neurological disorders. The differential diagnosis was carried out primarily with critical illness polyneuropathy. The authors emphasize the rarity of the presented case: to date, such a combination of pathologies has never been described in the literature.

Abstract—NF-κB is a family of nuclear transcription factors that play a leading role in the pathogenesis of many chronic inflammatory processes and in immune response regulation. At the end of the last century, NF-κB was mainly considered as a mediator of apoptosis in immune cells. Subsequent studies demonstrated its involvement in the development of the central nervous system, plasticity, neuronal differentiation, neurodegeneration, and brain injury. However, its role in the regulation of survival of mature CNS neurons in neuroinflammation proved controversial. This review summarizes the data on the involvement of NF-κB in the response of different brain cell types to the action of pro-inflammatory factors. Different subunits of the NF-κB family form dimers whose involvement in the regulation of gene expression depends on stimulus type. Interestingly, NF-κB is involved in the pro-inflammatory activation of microglia and astrocytes, whereas in neurons its protective or degenerative effects depend on the type of stimulus and on the time of the delayed cell response. The stimulus-dependent nature of NF-κB activation is determined by a wide range of receptors triggering a number of cell signaling cascades that terminate in the activation of the transcription factor. Tumor necrosis factor receptors (TNFR) or death receptors, Toll-like receptors (TLR), and protease-activated receptors (PAR) are among the membrane receptors capable of initiating intracellular cascades leading to the activation of NF-κB. Importantly, NF-κB activity and its effects can be modulated by other transcription factors. STAT1, STAT3, and Sirt1 are the molecules that, according to recent studies, are able to change the character of the NF-κB-mediated cellular responses. Thus, NF-κB is a transcription factor playing one of the key roles in determining the outcome of negative stimuli on the nervous system, which is why it may be considered as a pharmacological target for treating neurodegenerative processes associated with inflammation.

OBJECTIVE:To identify an effect of the neurohumoral response on the severity and orientation of Fas-ligand-initiated processes in the acute period of IS.MATERIAL AND METHODS:The study included 155 patients with IS in the territory of the left and right middle cerebral arteries, the control group consisted of 28 people. The National Institutes of Health Stroke Scale (NIHSS), the Hospital Anxiety and Depression Scale (HADS), and the Daily Life Stress scale were used. Concentrations of sFas, sFasL, cortisol (K), adrenaline (A), norepinephrine (NE), adrenocorticotropic hormone (ACTH) in the blood plasma of patients with IS were measured by enzyme-linked immunosorbent assay on days 1, 7 and 21 and once in the control group. CD3CD95+ lymphocytes phenotyping was performed using flow cytometry.RESULTS AND CONCLUSION:The hypothalamic-pituitary-adrenal axis dominance is associated with the activation of the apoptosis-inducing properties of peripheral blood in the first week after the IS onset and their decrease towards the end of the acute period, which is clinically represented by the increased levels of anxiety and depression, an unfavorable outcome of the acute period of IS.

Interleukin 6 (IL-6) plays an important role in the pathogenesis of ischemic stroke (IS), exerting a modulating effect on a number of processes that determine the outcome of this disease. Objective: to investigate the peripheral blood levels of IL-6 in patients in the acute period of different IS pathogenetic subtypes and its effect on recovery rates. Patients and methods. The study enrolled 155 patients (74 men and 81 women; mean age, 63.8 years). A control group consisted of 28 people without IS. Pathogenetic subtype II was established in accordance with the TOAST (Trial of Org 10172 in Acute Stroke Treatment) criteria on the basis of their clinical picture and the data of computed tomography or magnetic resonance imaging and ultrasonography of the main arteries of the head. The severity of a patient's condition and a focal neurological defect and the time course of clinical changes after stroke were determined using the National Institutes of Health Stroke Scale (NIHSS). An enzyme immunoassay (EIA) was used to measure IL-6 levels on days 1, 7, and 21 after onset of IS. An enzyme immunoassay (EIA) was used to measure IL-6 levels on days 1, 7, and 21 after onset of IS. Results. In the acute period of IS, there were significantly elevated levels of IL-6. The latter reached its highest values on day 7 in patients with the atherothrombotic pathogenetic subtype of IS. On day 7 of the study, the peak concentration of IL6 was typical for patients with all subtypes of IS, except for lacunar stroke. After its increase on day 1 of the study, the IL6 level in patients with lacunar stroke did not change significantly in all other periods. In acute IS, the concentration of IL-6 was significantly influenced by the following cardiovascular risk factors: hypercholesterolemia of days 1, 7 (p<0.01) and 21 (p<0.05), hypertension in day 1 (p<0.05), diabetes mellitus on days 1 and 7 (p<0.05), and coronary heart disease in all the study periods (p<0.01). The IL-6 concentration significantly correlated with the severity of neurological defect, but did not significantly affect the rate of recovery in the patient with acute IS. Conclusion. IL-6 was established to be of prognostic value for the outcome of acute IS on day 7. The rate of recovery can be used to identify targets for therapeutic intervention.

This paper presents a literature review considering the role and mechanism of apoptosis in the pathogenesis of ischemic stroke (IS). The authors introduce a new concept: the functional request of the patient as a set of external (the nature and intensity of rehabilitation measures, characteristics of everyday life, diet, etc.) and internal (genetic factors, internal picture of the disease, availability of rental and other psychological facilities and etc.) attributes. This concept allows a new angle in understanding the pathogenesis of IS and creates fundamental and clinical potential for more successful approaches to therapy and rehabilitation after IS.

AIMTo analyze the histological features of changes in the brain tissue after ischemic stroke.MATERIAL AND METHODSBrain tissue samples obtained in autopsy from 9 people died as a result of a left middle cerebral artery ischemic stroke from 3 to 7 days after admission were studied. Tissue samples were taken from 3 areas of the brain: 1) contiguous to the tissue necrotic damage site zone, 2) 5-10 cm distant from the previous one, 3) the contralateral hemisphere zone symmetrical to damage site. Samples were Nissl and hematoxylin-eosin stained. Detection of p53 protein, NSE, GFAP was performed by indirect immunoperoxidase immunohistochemistry.RESULTSA decrease in the total number of neurons and glial elements, their spatial redistribution, change in cell structure and their functional activity was found. The changes of the artery wall and impaired regional blood flow were detected. The more intense NSE reactivity; p53-positive neurons, reduced neuron-astrocytes distance were identified in zones 2 and 3.CONCLUSIONIschemic stroke is accompanied by severe histological changes. These changes with varying degrees of severity occur both in the areas adjacent to necrotic core, and in remote areas, and it is a substrate for neuroplasticity.

The purpose to identify key morphological features of the Astrocytes and Neurons in the acute local cerebral ischemia human cortex. Subjects and methods: Left middle cerebral artery ischemic stroke died persons (n = 9) brain tissue samples from 3 zones: 1st — contiguous to the tissue necrotic damage site zone, 2nd — 5—10 cm distant from the previous one, 3rd — the damage site symmetrical zone of the contralateral hemisphere. For GFAP, MAP-2, NSE, p53 detection indirect immunoperoxidase immunohistochemical staining method has been used. Also, the samples were Nissl and Hematoxylin-Eosin stained. Results. The most pronounced changes in the quantity and morphological structure of astrocytes and neurons are found in directly adjacent to the necrotic core region of theleft middle cerebral artery ischemic stroke brain. This indicates the prevalence of the inflammation processes around the area of nerve tissueischemic destruction. Morphological changes of neurons and astrocytes, apoptosis, enhanced neuron-astrocyte interaction found in the area bordering on necrotic core (5—10 cm from it), as well as ischemic hearth symmetrical sites of the contralateral hemisphere. This interaction is essential for the neuroplasticityrealization in the local ischemic brain injury. Conclusion. The results obtained were shown the nerve tissue morphological characteristics changes occur in local cerebral cortex ischemic injury not only in the lesion, but also in the contralateral hemisphere. These changes are probably related to the implementation of neuroplasticity.

The aim: to identify the relationship between the severity of psychovegetative and pain in women with dysmenorrhea. Patients and methods: 46 women (mean age 22.3±6.2 years old) with dysmenorrhea. 3 groups: mild, moderate and severe dysmenorrhea were distinguished as symptoms severity. Results. The correlations between the pain severity according to numerical pain intensity scale (NPIS) and the values of other parameters: with the anxiety severity Sheehan scores (r=0.644, p

The purpose to identify key morphological features of the Astrocytes and Neurons in the acute local cerebral ischemia human cortex.Subjects and Methods:Left middle cerebral artery ischemic stroke died persons (n = 9) brain tissue samples from 3 zones: 1st - contiguous to the tissue necrotic damage site zone, 2nd - 5-10 cm distant from the previous one, 3rd - the damage site symmetrical zone of the contralateral hemisphere. For GFAP, MAP-2, NSE, p53 detection indirect immunoperoxidase immunohistochemical staining method has been used. Also, the samples were Nissl and Hematoxylin-Eosin stained.Results:The most pronounced changes in the quantity and morphological structure of astrocytes and neurons are found in directly adjacent to the necrotic core region of theleft middle cerebral artery ischemic stroke brain. This indicates the prevalence of the inflammation processes around the area of nerve tissueischemic destruction. Morphological changes of neurons and astrocytes, apoptosis, enhanced neuron-astrocyte interaction found in the area bordering on necrotic core (5-10 cm from it), as well as ischemic hearth symmetrical sites of the contralateral hemisphere. This interaction is essential for the neuroplasticityrealization in the local ischemic brain injury.Conclusion:The results obtained were shown the nerve tissue morphological characteristics changes occur in local cerebral cortex ischemic injury not only in the lesion, but also in the contralateral hemisphere. These changes are probably related to the implementation of neuroplasticity.

The Fas system can promote several biological effects due to their activation after ischemic stroke: apoptosis, inflammation, proliferation, differentiation. Fas interacts with adapter proteins activating a number of signaling pathways, including MAPK, NFKB, JNK, ERK, phosphorylation of cytoskeletal proteins, and caspase-dependent apoptosis. Fas expressed by neuronal progenitor cells from the subventricular zone does not induce apoptosis in healthy adult humans. During motion and differentiation of these cells, Fas regulates their morphological structure by the phosphorylation/dephosphorylation of cytoskeletal elements. An increase in the Fas and Fas ligand expression is observed in response to stroke injury. Fas responsible not only for cell death and inflammation but also for neuronal plasticity which occupies a central place in the processes of sanogenesis.

The receptors, whose ligand interaction activation was previously considered to be associated with initiation of apoptosis only, can have a range of biological effects: apoptosis, inflammation, proliferation, and differentiation. Therefore, interaction between death receptor and its ligand does not always mean the initiation of programmed cell death and blocking of this ligand-receptor interaction can affect the initiation of recovery and neuroplasticity mechanisms. Fas is one of these death receptors. The following review represents data on the conditions of Fasdependent signal pathways induction in ischemic stroke. There is a possibility for the development of new target neuroprotective drugs with selective effects on different separated signal pathways, activated by ligand-receptor interactions in Fas-FasL (Fas ligand) system.

The goal of the present study was to investigate the plasma levels of sTNF-alpha, sTNF-R1 in acute stroke patients, to study the relation between ones, the neurological stroke severity and functional disability. The investigations comprised 60 ischemic stroke patients, 25 patients form control group. Plasma levels of sTNF-alpha, sTNF-R1 were detected by means of ELISA. The conclusion of interaction of sTNF-alpha and tmTNF-R1 increases inflammatory and apoptotic brain tissue damage on the first day of stroke is drawn. On the 7-th and 21-st days of stroke sTNF-alpha realize a neuroprotective effect. The interaction sTNF-alpha and sTNF-R1 blockade of damage expansion. As the result, prognostic significance of sTNF-alpha/sTNF-R1 is showed.