[Primary diffuse meningeal melanomatosis: a literature review and a case report]. / Pervichnyi diffuznyi melanomatoz myagkoi mozgovoi obolochki: obzor literatury i sobstvennoe nablyudenie.

Primary melanocytic tumors of the central nervous system (CNS) are extremely rare and account for only 1% of all melanomas and 0.05% of primary brain tumors. In case of diffusely invasive lesions of the pia mater with a tumor of melanocytic origin (without signs of extracranial metastases), the tumors are classified as primary diffuse meningeal melanomatosis (PDMM). The latter is an extremely rare subtype of CNS malignant tumor with an incidence rate of 1 in 20 million people. Despite the development of neuroimaging techniques, today a morphological examination remains the main and most accurate method for verifying CNS melanocytic tumors. The paper describes a fatal case of PMMD manifested as epileptic syndrome, with a rapidly progressive course.

[Chordoma as a neurosurgical pathology]. / Khordoma kak neirokhirurgicheskaya patologiya.

OBJECTIVE: Assess the significance of chordoma as a neurosurgical pathology, taking into account the latest edition of the WHO classification of soft tissues and bone tumors (2020). MATERIAL AND METHODS: An analysis of 28 chordomas was carried out. All chordomas were histologically verified, including using immunohistochemical markers of notochordal differentiation (S100, EMA, keratin, brachiuria protein). RESULTS: Patients with chordomas accounted for 0.25% of the total number of neurosurgical patients. The vast majority (27) of chordomas had a cranio-vertebral localization. Sacral localization (S3-S5) of the tumor was detected in 1 patient. In 4 (15%) cases, operations were performed for the recurrence of chordoma. The tumors tended to grow into the structures of the skull, overgrown the vessels and nerves, and compress the adjacent brain structures. This was manifested by pain syndrome, neurological symptoms, impaired liquorodynamics. According to histopathological criteria, 27 (96%) cases of tumors were classified as conventional (usual) chordoma type, among them 7 corresponded to the chondroid subtype of the chordoma. In 1 case (4%), a dedifferentiated chordoma was detected. CONCLUSION: Chordoma, due to its axial localization, naturally involves adjacent structures of the nervous system, has clinically significant neuropathological manifestations, and often provides direct indications for a special neurosurgical approach. This requires its consideration not only as a bone, but also as a neurosurgical oncological pathology, along with other non-meningothelial (mesenchymal) tumors of the CNS.

[Isolated sarcoidosis of the brain]. / Izolirovannyi sarkoidoz golovnogo mozga.

Sarcoidosis is a granulomatous multisystem disease of unclear etiology. Among the many local lesions of different localization, lesions of the central and peripheral nervous system (neurosarcoidosis) are distinguished as particularly unfavorable manifestations of the disease. Only in rare cases, neurosarcoidosis can manifest as isolated or primary. Biopsy remains the gold standard for the diagnosis of neurosarcoidosis. However, significant difficulties remain in verifying the diagnosis, especially with an isolated variant of the lesion A rare case of isolated neurosarcoidosis with a primary focus in the right hemisphere of the brain is described. The data of histological, histochemical and immunohistochemical examination of the surgical material are presented.

[Morphological evaluation of the effectiveness of fluorescence navigation with chlorin e6 in surgery for malignant gliomas]. / Morfologicheskaya otsenka effektivnosti fluorestsentnoi navigatsii s khlorinom e6 v khirurgii zlokachestvennykh gliom.

OBJECTIVE: To evaluate the effectiveness of fluorescence navigation with chlorin e6 in surgery for malignant gliomas based on surgical material morphological and immunohistochemical data. MATERIAL AND METHODS: The surgical material obtained from patients with high-grade (Grade III-IV) anaplastic glioma was examined. Along with histological examination, the proliferation marker Ki-67, the cell cycle transcription factor protein p53, and vascular endothelial growth factor (VEGF) were determined. RESULTS: A significant direct correlation was found between the expression of Ki-67, p53, and VEGF and the fluorescence intensity of tumor tissues (p<0.05). CONCLUSION: The technique of fluorescence navigation using chlorin e6 in comparative morphopathological analysis has confirmed its effectiveness in surgery for malignant gliomas.

[Structural heterogeneity of epileptic foci in local drug-resistant epilepsy]. / Strukturnaya geterogennost' epilepticheskikh ochagov pri lokal'noi farmakorezistentnoi epilepsii.

BACKGROUND: To study etiopathogenesis is one of the most important tasks of modern neurology. Various types of structural changes occur in drug-resistant epilepsy (DRE); however, they are described as distinct phenomena. OBJECTIVE: To provide a comprehensive characterization of structural changes in the cortex and adjacent white matter in the electrophysiological activity zone (in the epileptic focus) in patients undergoing surgery for DRE. MATERIAL AND METHODS: Biopsy material of fragments of the temporal lobe and hippocampus from 16 patients aged 21 to 54 years (mean age, 25 years) with DRE were intraoperatively obtained at the Prof. A.L. Polenov Russian Research Institute of Neurosurgery. The investigators studied histological sections stained with H&E, toluidine blue according to the Nissl method and the Spielmeyer method, as well as the results of immunohistochemical reactions with glial fibrillary acidic protein (GFAP), vimentin, and neurofilaments (NF) (Dako antibodies, Denmark). RESULTS: Histological examination revealed a set of heterogeneous changes, reflecting the complex pathogenetic interactions that developed during the formation of an epileptic focus. Structural brain damage involved both gray and white matter. Focal cortical dysplasia was diagnosed in 14 (87.5%) cases; white matter neuronal heterotopia in 100%; neuronal reactive and destructive changes in 100%; epileptic leukoencephalopathy (vascular demyelination, microcysts, sclerosis and dystonia, gliosis) in 100%, cortical atrophy in 12.5%, and hippocampal sclerosis in 20% (in 2 out of the 10 examinees). CONCLUSION: The morphopathological heterogeneity in the structure of epileptic foci reflects the complexity of etiopathogenetic interactions, the polymorphism of epileptic manifestations, and the individual nature of formation of the epileptic system, which requires an integral approach to understanding the pathogenesis and morphogenesis of formation of the epileptic system and provides a direction for a personalized approach to epilepsy treatment.

Role of Protein Kinase Akt Activation in Protective Effect of Ganglioside GM1 on PC12 Cells Exposed to H2O2.

Micro- and nanomolar concentrations of ganglioside GM1 improved viability of neuronal PC12 cells under conditions of oxidative stress and reduced H2O2-induced ROS accumulation in these cells. These effects were more pronounced at micromolar concentrations. GM1 in concentrations of 100 nM and 10 µM significantly and substantially increased basal activity of protein kinase B (Akt) (the level of phosphorylated Akt form), but had virtually no effect on its expression in PC12 cells. In the presence of PI3K inhibitor LY294002 preventing protein kinase Akt activation, the protective effect of GM1 significantly decreased. These findings suggest that activation of protein kinase Akt by GM1 contributes to improvement of PC12 cell viability by this ganglioside.

[Granulomatous inflammation in the bed of resected cerebral cavernoma in a child, caused by a hemostatic agent].

OBJECTIVE: The study presents a clinical observation of foreign body granuloma, which is rare productive inflammation, developed on treatment with a hemostatic material upon removal of cerebral cavernoma. MATERIAL AND METHODS: A 4-year-old boy operated on for left parietal lobe cavernoma was diagnosed with a mass lesion during a follow-up MRI examination 4 months after surgery. The patient was re-operated in connection with suspected abscess formation. The pathological tissue was subjected to the histological and immunohistochemical examination. RESULTS: Inflammation was accompanied by the formation of foreign body granulomas, and, in some areas, had immune nature with signs of focal destructive vasculitis, delayed maturation of the granulation tissue, and disturbance of the current organization and encapsulation processes. It is worth noting that granulomatous inflammation around a hemostatic material in the brain has no specific features during introscopy and mimics an abscess or tumor recurrence. CONCLUSION: The use of hemostatic materials upon resection of cerebral cavernous malformations may cause formation of granuloma mimicking disease relapse or abscess in the long term period. To prevent granulomatous inflammation, removal of a hemostatic material, if possible, from the surgical field is recommended when reliable hemostasis is achieved.

[THE DIFFERENTIAL DIAGNOSTIC OF ANEMIA].

The article presents analysis of the publications' data of the recent years concerning regulation of iron metabolism and possibilities of application of indicators of iron metabolism in differential diagnostic of anemia. The original results of protein detection are described concerning bivalent transporter of metals and ferroportine under iron-deficiency anemia, anemia of chronic inflammatory diseases and autoimmune hemolytic anemia. The significance of these proteins in more profound comprehension of pathogenesis is demonstrated

Α-tocopherol prevents ERK1/2 activation in PC12 cells under conditions of oxidative stress and its contribution to the protective effect.

Preincubation with 100 nM and 100 µM α-tocopherol for 18 h prevented long-term activation of extracellular signal-activated kinase (ERK1/2), induced by H2O2in PC12 cells. α-Tocopherol significantly reduced H2O2-induced death of PC12 cell, but its protective effect was significantly lower in the presence of ERK1/2 inhibitor. These data show that prevention of long-term activation of ERK1/2 by α-tocopherol contributes to the increase in viability of PC12 cells exposed to H2O2. This fact suggests that inhibition of ERK1/2 activity by α-tocopherol reduces neuronal cell death in the brain under conditions of oxidative stress in vivo.

[A rare case of glioblastoma metastasis to the lung].

The paper describes a case of metastatic glioblastoma in a 64-year-old woman who died in the early postoperative period after tumor removal. Lung metastases were diagnosed at autopsy. The tumor invading the superior sagittal sinus, a large venous reservoir shunting blood to the superior vena cava, was a factor contributing to extracranial extraneural hematogenous dissemination of the tumor in this case.

[Metabolic effects of ganglioside GM1 on PC12 cells at oxidative stress depend on modulation of activity of tyrosine kinase of trk receptor].

Evidence has been obtained that only GM1, but also other main brain gangliosides (GD1a, GD1b, and GT1b) increase viability of ells of the PC12 neuronal line submitted to action of H2O2. By the example of GM1 and GD1a, gangliosides have been shown to induce a protective effect when acting on PC12 cells under conditions of oxidative stress both at micro- and nanomolar concentrations that are physiological concentrations of gangliosides in cerebrospinal fluid. It has been shown for the first time that GM1 at nanomolar concentrations decrease the H2O2-induced formation of reactive oxygen species (ROS). It was found that in the presence of K-252a, an inhibitor of tyrosine kinase of Trk receptors, GM1 at concentrations of 10 microM and 10 nM lost the ability to increase viability of these cells under conditions of oxidative stress. The dependence of protective and metabolic effects of ganglioside GM 1 in PC 12 cells at action on them of H2O2 on modulation of activity of tyrosine kinase of Trk receptors (i. e., on the same signal system) agrees with concept of the essential role of the GM1 antioxidant effect in its increase of cell viability.

[Antiapoptotic effect of alpha-tocopherol at micro- and nanomolar concentrations on cells of neuronal line PC12 according to data of flow cytometry].

By the method of flow cytometry it has been shown that alpha-tocopherol at micromolar concentrations produces antiapoptotic effect on the PC12 neuronal line cells exposed to the toxic agent hydrogen peroxide at various terms of incubation with it. At the same time, alpha-tocopherol at nanomolar concentrations had protective (antiapoptotic) effect only after the long (18 h) preincubation of the PC12 cells with it prior to exposure to hydrogen peroxide. This seems to indicate that the alpha-tocopherol effect at these concentrations is mediated by a signal transduction system.

[Dependence of protective effect of alpha-tocopherol on its concentration and time of action on PC12 cell under conditions of oxidative stress].

At the short-term incubation (0.5 and 1.5 h) of cells of the PC12 neuronal line with alpha-tocopherol, its protective effect against the cytotoxic hydrogen peroxide action was increased with rise of its concentration in samples; the protection was practically absent at action of nanomolar antioxidant concentrations, but was well expressed at its micromolar concentrations. These data agree with the concept that alpha-tocopherol increases the cell living activity by reacting directly with free radicals, which leads to formation of the less reactive compounds deprived of non-paired electron. The evidence is obtained that at the long-term action on PC12 cells, alpha-tocopherol not only in micro-, but also in nanomolar concentrations increases statistically significantly the cell living activity under conditions of oxidative stress. As follows from the obtained data, an important role in realization of the alpha-tocopherol protective effect at the long-term incubation with it seems to be played by modulation by this antioxidant of activity of protein kinase activated by extracellular signaling, phosphatidylinosite 3-kinase, and protein kinase C.

[Role of tyrosine kinase of Trk-receptors in realization of antioxidant effect of ganglioside GM1 in PC12 cells].

Ganglioside GM1 has been shown to increase viability of PC12 cells at their induction of oxidative stress by hydrogen peroxide. However, in the presence of inhibitor of tyroxine kinase Trk-receptors K-252a this GM1 effect decreases or virtually disappears. To understand mechanism of the protective effect, there was studied action of H2O2, GM1, and inhibitor K-252a on formation of reactive oxygen species (ROS). It has been shown that ganglioside GM1 decreases significantly the H2O2-induced ROS accumulation in PC12 cells; however, in the presence of inhibitory of tyrosine kinase of Trk-receptors, this GM1 effect is not revealed. It has been found that inhibitors of each of protein kinases present at the signal realization stages following the stages of activation of tyrosine kinase Trk-receptors--Erk 1/2, PI3-kinases, and PKC, decreased the GM1 ability to reduce the H2O2-induced ROS accumulation, while in the combined use of inhibitors of these three protein kinases, the GM1 effect was completely absent. Thus, the ganglioside GM1 antioxidant effect on PC12 is mediated by activation of tyrosine kinase Trk-receptors and protein kinases perceiving signal from this enzyme.

[Metastatic glioblastoma in a submandibular lymph node (a rare case)].

Extraneural metastases from glioblastoma are rare. A case of metastatic right parietal lobe glioblastoma in cervical node after repeat craniotomy is presented.

[Atopic dermatitis in teenagers as medical and social problem for the Armed Forces].

The analyze of data of official statistics of Department of Health and Social Development speaks for veridical differences in prevalency and morbidity of atopic dermatitis by teen-agers in comparison with children (younger then 14 years old). These indexes are higher in 2-3 times, then these indexes among children. For the first time was effectuated the analyze of health survey. It has been found that in structure of dermatological pathology in general 5/6-3/4 is the group with patients with new-onset diagnosis, and only 1/5-1/4 - is a dispensary group. For children, persons older then 18 and population in general the index of health survey is practically identic and is equal to 0.5. For teen-agers this index is higher - 0.6 and more. The highest abundance and morbidity is: among constituents of the Russian Federation - Privolzhsky Federal district, among it's regions - Ul'yanovsk region.

[A decrease of neuroprotector effect of ganglioside GM1 on PC12 cells under conditions of oxidative stress in the presence of inhibitor of tyrosine kinase of Trk-receptors].

Effects of inhibitors of tyrosine kinases (K-252a, genistein) and of phospholipase A2 (bromophenacetyl bromide) on viability of PC12 cells are studied in the presence of hydrogen peroxide and ganglioside GM1. The degree of inhibition of hydrogen peroxide cytotoxic effect by ganglioside GM1 amounted to 52.8 +/- 4.3 %. However, in the presence in the medium of 0.1 and 1 microM inhibitors of tyrosine kinase of Trk-receptors (K-252a) it was as low as 32.7 +/- 6.5 % and 11.7 +/- 9.8 %, respectively. GM1 prevented Na+, K+-ATPase produced by H2O2, but in the presence of 1 microM K-252a this effect was practically not pronounced. In the presence of another inhibitor of tyrosine kinases--genistein, a tendency for a decrease of the GM1 protective effect was observed at its concentrations 0.1 and 1 microM, whereas at a higher concentration 10 microM genistein depressed the GM1 neuroprotective effect statistically significantly. It was found that inhibitor of phospholipase A2 bromophenacetyl bromide did not affect the action of GM1 aimed at increasing the viability of cells under action of hydrogen peroxide on them. It seems that this enzyme is not involved in the cascade of reactions participating in realization of the ganglioside protective effect. Thus, inhibitor of tyrosine kinase of Trk-receptors K-252 decreases or practically prevents the ganglioside GM1 neuroprotective effect of PC12 cells under stress conditions; the same ability is characteristic of genistein--an inhibitor of tyrosine kinases of the wider spectrum of action.

[PC12 cells transfected with human mutant gene causing one of Alzheimer's disease forms have a high sensitivity to oxidative stress].

Used in this work are PC12 cells transfected with human gene expressing amyloid precursor protein of beta-peptide and carrying the so-called "Swedish mutation" leading to the appearance of one Alzheimer's disease family forms. It has been shown that the PC12 cells transfected with this mutant gene, at action of various hydrogen peroxide concentrations, die to the significant greater degree than the used for comparison PC12 cells transfected with analogous human gene of the wild type or than vector-transfected cells. It has been found that ganglioside GM1 at micro- or nanomolar concentrations is able to increase viability of the PC12 cells transfected with the mutant gene causing a significant accumulation of endogenous amyloid beta-peptide. The obtained data confirm an important role of oxidative stress in injury and death of brain nerve cells in Alzheimer's disease.