[Transcription Factors of Direct Neuronal Reprogramming in Ontogenesis and ex vivo].

Direct reprogramming technology allows several specific types of cells, including specialized neurons, to be obtained from readily available autologous somatic cells. It presents unique opportunities for the development of personalized medicine, from in vitro models of hereditary and degenerative neurological diseases to novel neuroregenerative technologies. Over the past decade, a plethora of protocols for primary reprogramming has been published, yet reproducible generation of homogeneous populations of neuronally reprogrammed cells still remains a challenge. All existing protocols, however, use transcription factors that are involved in embryonic neurogenesis. This is presumably be the key issue for obtaining highly efficient and reproducible protocols for ex vivo neurogenesis. Analysis of the functional features of transcription factors in embryonic and adult neurogenesis may not only lead to the improvement of reprogramming protocols, but also, via cell marker analysis, can exactly determine the stage of neurogenesis that a particular protocol will reach. The purpose of this review is to characterize the general factors that play key roles in neurogenesis for the embryonic and adult periods, as well as in cellular reprogramming, and to assess correspondence of cell forms obtained as a result of cellular reprogramming to the ontogenetic series of the nervous system, from pluripotent stem cells to specialized neurons.

[Headache in the population of schoolchildren: prevalence, pattern, risk factors].

The paper discusses the prevalence, pattern, and risk factors of childhood headache (HA) according to questionnaire data from 1074 general educational school pupils. Periodic HA was reported by 42.1% of the children. There was a preponderance of exercise-induced HA (30.6%) and migraine (7.8%). There was an age and gender determination of childhood HA frequency; there was a predominance of chronic exercise-induced HA, migraine, and their concomitant forms in female adolescents. There was a high comorbidity of primary HA with other psychosomatic disorders mainly with autonomic dysfunction and emotional disorders. The risk factors for chronic HA were a poor family history (familial psychogenias, pain family history, low'socioeconomic status family), and school stress. The clinical form of cephalgia, comorbidities, and predictive factors should be taken into account to prevent and treat HA. The use of the international diagnostic criteria developed by the experts of the HA Association is of cardinal importance in improving the diagnosis of childhood HA.

[Infections and inflammation in the development of stroke]. / Infektsii i vospalenie v razvitii insul'ta.

The review systematizes data on the role of infectious diseases and systemic inflammation in the pathogenesis of stroke. Various risk factors for stroke associated with pro-inflammatory reactions and their contribution to the pathogenesis of cerebrovascular pathology are analyzed. The interaction of systemic inflammation with hemostasis disturbances and clots formation, activation of autoreactive clones of cytotoxic lymphocytes, the progression of endothelial damage, and other processes is shown. Along with infection, these factors increase the risk of stroke. The key mechanisms of the pathogenesis from the development of acute or chronic inflammation to the preconditions of stroke are presented. The mechanisms of the acting of the infectious process as a trigger factor and/or medium-term or long-term risk factors of stroke are described. A separate section is devoted to the mechanisms of developing cerebrovascular diseases after COVID-19. Identifying an increased risk of stroke due to infection can be of great preventive value. Understanding of this risk by specialists followed by correction of drug therapy and rehabilitation measures can reduce the incidence of cerebrovascular complications in infectious patients.

['Stroke chameleons']. / 'Insul'ty-khameleony'.

The diagnosis of acute stroke should be correct and early that allows physician planning the most effective treatment strategies (reperfusion therapy, undifferentiated (basic) treatment, early secondary prevention). However, stroke symptoms can be atypical and similar to some other (non-vascular) event. It can significantly complicate the clinical diagnosis of stroke and decrease the patient's chances for effective treatment. A stroke should be suspected in every patient with acute onset of neurological symptoms, especially when the patient has the 'vascular' risk factors. Furthermore it is important to remember that negative CT-scan data and/or MRI data do not exclude the presence of not only ischemic stroke but also hemorrhagic stroke. The article describes the main variants of strokes with atypical symptoms (strokes-chameleons), emphasizes the importance of careful clinical examination, provides supportive differential diagnostic criteria and discusses limitations of neuroimaging methods.

[Immunoenzyme analysis of ferritin in diagnosing brain tumors]. / Immunofermentnyi analiz ferritina v diagnostike opukholei golovnogo mozga.

A procedure was developed to purify ferritin from the human brain tissue. The preparation is a heavy chain of ferritin. The level of ferritin in biological fluids was evaluated using the sandwich solid-phase immunoassay. This fraction of ferritin was found in the cerebrospinal fluid of patients with brain tumors. Content of the ferritin heavy chain in cerebrospinal fluid correlated with the rate of brain tissue malignancy.

[Criteria of efficiency of transplantation of embryonic nervous tissue preparations in rats with 6-OHDA-impaired dopaminergic nigrostriatal system]. / Kriterii éffektivnosti transplantatsii preparatov émbrional'noi nervnoi tkani u krys s povrezhdeniem dofaminergicheskoi nigrostriarnoi sistemy 6-gidrooksidofaminom (6-OHDA).

Effectiveness of transplantation of cells from embryonal nervous tissue of the ventral mesencephalon (VM ENT) and striatum (STR ENT) by apomorphin-induced motor asymmetry (APO-test), consolidation of the transplant (the degree of glyal reaction and amount of dopaminergic neurons) and blood serum levels of GFAP was studied for 3 months in Wistar rats with 6-OHDA-impaired dopaminergic nigrostriatal system. Marked therapeutic effectiveness was registered in VM ENT transplantation in the denervated striatum and in combined transplantation of VM ENT into the lateral cerebral ventricle simultaneously with STR ENT transplantation in the striatum. Separate transplantation of VM ENT in the lateral ventricle and STR ENT in the striatum had no positive effect on recovery of the dopaminergic nigrostriatal system. A correlation was found between the degree of glial reaction of ENT transplants, severity of rotation asymmetry and serum levels of gliofibrillary protein (GFAP). GFAP in the serum for lifetime assessment of transplant consolidation and prognosis of neurotransplantation efficiency was assayed.

[Peculiarities of the development of cerebral blood circulation disturbances in patients with chronic cardiac insufficiency].

One hundred and one patients with chronic cardiac insufficiency due to postinfarction cardiosclerosis have been examined. Clinical studies, echocardiography, duplex scanning of brachiocephal arteries were conducted. As the left ventricular (LV) is remodeled corresponding to a stage of chronic cardiac insufficiency (an increase of systolic and diastolic LV volumes, and myocardial mass, a decrease of ejection fraction), structural changes in the wall of extra- and intracranial vessels (the increase of intima-media complex and alteration of vessel geometry) increase and the cerebral dynamics (the decrease of systolic and volume velocities of blood flow) worsens. The negative dynamics of hemodynamic indices is accompanied by the intensification of neurologic symptoms of chronic cardiac insufficiency.

[Leprous neuropathies]. / Leproznye nevropatii.

The damage to the peripheral nervous system (PNS) is a marker of Micobacterium leprae (M. leprae) infection that develops as a result of the M. leprae invasion to the Schwann cells. Clinical, functional (skin-deep and stimulating electromyography, determination of the spreading velocity of the pulsatory wave along the arteries of muscle type, direct and volumetric sphingmography, reovasography, skinning electrotermometry) and immunological (evaluation of antibodies to neuroantigenes by ELISA) methods were used to study 132 patients with leprous neuropathy. Sensory impairment (descend of superficial sensibility, combination of the spotted, trunk and polyneuritic types of sensory injury), hypertrophy of the peripheral nerves and their painfulness by palpation were shown to develop at the initial stage, with the following joining of motor and trophic disturbances, such as amyotrophy, contractures, shortening of digits, trophic ulcer. Skin-deep and stimulating electromyography revealed the subclinical manifestation of neuromuscular system injuries in clinically normal muscles. A neuroantigen's entrance into the bloodstream and antibody reactions to them were characteristic of LN. High antibody levels, as a rule, corresponded to the exacerbations of leprous neuropathy, activation of leprous process, relapses of the disease and reactions of leprous erythema nodosum type. An association between specific humoral response to the antigens of the M. leprae and production of the antibodies to neuromarkers was found.

[Chronic posttraumatic headache in juveniles]. / Khronicheskaia postravmaticheskaia golovnaia bol' u podrostkov.

The paper presents a comparative analysis of biologic, social-culturological and psychological factors of the premorbid, peculiarities of personality as well as the conditions of getting a slight craniocerebral trauma (CCT) as well as the therapy in the acute period and a psychosocial situation during 1 year after the trauma in juveniles with chronic posttraumatic headache (PTH) (74 individuals) and without it (24 cases). As the main clinical variation of a chronic PTH was chronic PTH of tension, we studied comparative anamnestic data and peculiarities of personalities in 22 juveniles with a chronic headache of tension without PTH in the anamnesis. It was found common pathogenetic mechanisms of the development of both traumatic and non-traumatic cephalgias; the risk factors of PTH chronicity were identified, that was quite necessary for the elaboration of effective rehabilitation programs.

Structure of vascular plexuses of brain ventricles in ontogeny under normal conditions and in hypoxia.

The structure of vascular plexuses of brain ventricles in newborns developed under hypoxic conditions does not correspond to gestational age. Chronic hypoxia decreases activity of succinate dehydrogenase and iron content in vascular plexuses of brain ventricles.

[Clinical and psychophysiological characteristics of headache in childhood]. / Klinicheskaia i psikhofiziologicheskaia kharakteristika golovnoi boli v detskom vozraste.

Complex clinical psychophysiological as well as neurophysiological examinations of 210 children with migraine, chronic tension headache (CTH) and chronic posttraumatic headache (CPH) were carried out. Detailed comparative description of cephalalgia types is presented. In a CPH structure, predominates CTH (77.5%), combined type (14.1%); migraine (5.7%) and cervicogenic cephalalgia (2.7%) occur less often. CPH development mechanisms do not principally differ from non-traumatic cephalalgia pathogenesis. Trauma plays a role of a non-specific trigger in realization of these mechanisms. Chronic cephalalgia is caused mainly by poor social and psychological factors and patient's personality peculiarities. Psychovegetative syndrome in children with CTH, migraine or CPH reflects non-specifically diencephal structure disintegration; its clinical signs depending more on child's age than on cephalalgia type.

[The immunochemical indices of the structural damage to brain tissue at different periods of traumatic brain disease]. / Immunokhimicheskie pokazateli strukturnogo povrezhdeniia mozgovoi tkani v razlichnye periody travmaticheskoi bolezni golovnogo mozga.

Interorganic and neurospecific liquor proteins were measured in brain injury patients using enzyme immunoassay and radioimmunoassay (maximum sensitivity 2.0 and 0.05-1 ng/ml, respectively). The protein concentrations were found to vary with the time which elapsed since the injury.

Immunoenzyme assay of glial fibrillary acidic protein for evaluation of functional activity of cell grafts from embryonic ventral mesencephalon in rats with experimental hemiparkinsonism.

The relationship between the release of glial fibrillary acidic protein (GFAP) into systemic circulation and the efficacy of transplantation of embryonic nervous tissue was studied on rats with 6-OHDA-induced hemiparkinsonism. It was found that intrastriatal transplantation of cell preparations from embryonic ventral mesencephalon significantly attenuated apomorphine-induced rotation, which points to functional recovery of the dopaminergic nigrostriatal system. The degree of this recovery depends on reactive astrogliosis around the graft and survival of dopaminergic neurons. Analysis of GFAP concentration revealed significant elimination of this antigen into the circulation 7 and 14 days after transplantation. In rats with good consolidation of the graft without pronounced reactive gliosis, the concentration of GFAP reached 253.99+/-79.30 ng/ml on week 4 after transplantation and decreased to 8.2+/-3.3 ng/ml 8-12 weeks after transplantation. In rats with poor graft consolidation associated with death of transplanted neurons and gliosis in the graft and surrounding tissue the concentration GFAP increased to 476.4+/-111.0 ng/ml within 4 weeks after transplantation and remained elevated (235.0+/-44.8 ng/ml) for 12 weeks. Thus, monitoring of serum GFAP concentrations allows in vivo evaluation of the functional state of intracerebral graft and the level of reactive gliosis. This test can be used for the prognosis of transplantation efficacy.

Complex analysis of efficiency of transplantation of embryonic nerve tissue to rats with hemiparkinsonism.

Effect of transplantation of embryonic ventral mesencephalon preparation containing dopaminergic neurons on repair of the dopaminergic nigrostriatal system was studied in rats with hemiparkinsonism induced by 6-hydroxydopamine. Transplantation of embryonic ventral mesencephalon into denervated striatum led to a more than 50% decrease in apomorphine-induced rotation, recovery of dopamine and DOPAC levels in the brain, and to an increase in DOPAC excretion and the DOPAC-dopamine ratio in daily urine of rats with hemiparkinsonism. Dopaminergic neurons of the transplant survived, forming a network of tyrosine hydroxylase-positive processes growing beyond the transplant and reinnervating the adjacent compartments of the striatum. A positive correlation between urinary excretion of DOPAC and brain concentration of dopamine was revealed in denervated rats after transplantation of ventral mesencephalon. Intrastriatal transplantation of cell preparations of embryonic striatum containing no dopaminergic neurons and isolated local injury to the striatum did not affect regeneration of the denervated nigrostratal system.