[The dynamics of markers of apoptosis in the acute period of ischemic stroke]. / Dinamika markerov apoptoza v ostrom periode ishemicheskogo insul'ta.

AIM: To study the dynamics of markers of apoptosis (Bcl-2, p53) in serum in the acute period of ischemic stroke (IS) in comparison to the severity of the neurological condition and the volume of infarct. MATERIAL AND METHODS: Fifty-one patients (mean age 60.5±2.2 years) with the first ever carotid IS were examined within the first 24 hours. The comparison group consisted of 20 patients (mean age 58.7±2.1 years) with chronic cerebral insufficiency. Clinical and neurological dynamic examinations with assessment of neurological deficit using (NIHSS), CT/MRI of the brain; ELISA immunoassay of p53 and Bcl-2 in blood serum were carried out. RESULTS AND CONCLUSION: Significantly higher levels of p53 and of Bcl-2 were shown on the 3rd and 10th days in patients with IS compared to the control group (p<0.05). An increase in the content of p53 was positively correlated with the severity of neurological deficit (NIHSS≥10) on the first and third days of acute IS and with larger amounts of damage to the brain parenchyma according to the MRI study from the first day of IS and all subsequent days. High levels of Bcl-2 were positively correlated with the large volume of brain damage only on the 10th day of IS (p<0.045). The results confirm the active involvement of pro- and antiapoptotic processes in the formation of delayed neuronal death in the brain, which are important components of damaged brain tissue in IS.

[Risk assessment of thrombotic events in patients with schizophrenia and schizoaffective disorder in the acute state: the 'fibrinodynamics' technology]. / Otsenka riska tromboticheskikh narushenii u bol'nykh shizofreniei i shizoaffektivnymi rasstroistvami v ostrom periode bolezni s ispol'zovaniem tekhnologii 'fibrinodinamika'.

AIM: To assess the risk of thrombotic events in patients with schizophrenia and schizoaffective disorder based on 'fibrinodynamics' technology. MATERIAL AND METHODS: A group of 76 women, including 38 with paranoid schizophrenia (F20.0), 18 with schizoaffective disorder (F25.1) in the acute stage, and 20 healthy controls, participated in the study. The technology includes the study of coagulation and fibrinolysis, Karmin author software, and calculation of peak time and hemostasis potential of spontaneous clots. Growth and lysis of fibrin clots were studied in plasma purified from platelets. All preanalytic procedures were conducted within 30 minutes after blood sampling. Blood serum was studied separately using the neuroimmunological test. Dynamic of brightness profiles of the clots was determined and a number of parameters (peak time and hemostasis potential of spontaneous clots) were calculated using the Karmin software. RESULTS: In patients with schizophrenia, the dynamic brightness profile of the clots has two peaks: the first peak is formed as a result of the growth and lysis of the clot initiated by the activator, the second peak is due to the growth and lysis of spontaneous clots in the volume of the measuring cuvette far from the activator. In healthy donors, the second peak under experimental conditions is absent. In the group of schizophrenic patients, a strong negative correlation is observed between the peak time of the second peak and the activity of leukocyte elastase (Spearman R = -0.75, p<0.0001), i.e. the greater the activity of elastase, the earlier the maximum of the second peak is formed and vice versa. In the control group, there is no such correlation. Evaluation of the potential of hemostasis of spontaneous clots showed that in 42% of schizophrenic patients this parameter is shifted above the norm, which indicates an increased risk of thrombosis of small brain arteries in these patients. CONCLUSION: The developed technology of 'fibrinodynamics' has a good potential for introduction into personalized medicine to identify increased risks of thrombosis of small cerebral vessels in patients with acute schizophrenia leading to the development of cognitive disorders and to control the normalization of hemostasis with antiplatelet or anticoagulant drugs.

[Inflammatory and autoimmune reactions in different forms of nervous system functioning disorders].

Parameters of innate (the leukocyte elastase (LE) and alpha1-proteinase inhibitor (α-1-PI) activity) and adaptive immunity (the level of autoantibodies to neuroantigens nerve growth factor (NGF) and myelin basic protein (MPB)) were studied over time in the blood serum of 107 children with perinatal hypoxic-ischemic encephalopathy; 188 children with autism spectrum disorder; 108 patients with schizophrenia. The correlations between immunological parameters and clinical status assessment in all groups of patients using psychometric scales were analyzed. The involvement of innate immunity, i.e. inflammatory reactions, in pathogenesis of all analyzed forms of nervous system functioning disorders was confirmed. The activation of adaptive immunity, i.e. autoimmune reactions, was found only in the group of patients with the most severe forms of nervous system functioning endogenous disorders. The results indicate that the inflammatory and autoimmune reactions are pathogenic mechanism of all studied forms of nervous system functioning disorders.

[Serum immunological markers as predictors of effectiveness of antipsychotic therapy in patients with schizophrenia].

Serum immunological parameters - activity of leukocyte elastase (LE) and a1-proteinase inhibitor (a1-PI), content of C-reactive protein, von Willebrand factor, interleukin 8 as well as a level of autoantibodies to neuroantigens (nerve growth factor and basic myelin protein) were studied in patients with schizophrenia during their treatment with psychotropic drugs. All parameters studied differed in the groups of patients and controls. However, the pronounced dynamics was found only for LE and a1-PI activity. After the therapeutic course, the reduction of LE activity accompanied by the increase of a1-PI activity was observed. The correlation study between the biological parameters during disease exacerbation and therapeutic effectiveness assessed by the PANSS scores revealed that activity of LE and a1-PI may be considered as a prognostic marker of therapeutic efficacy, i.e. the high enzyme activity at the moment of maximal activity of the process was predictive of good therapeutic response.

Influence of high level of antibodies to myelin basic protein in female mice on the postnatal development and behavioral reactions of the progeny.

Physical development, behavioral reactions, and training capacity were studied in the progeny of female BALB/c mice with high levels of antibodies to myelin basic protein. The proposed protocol of immunization ensures high levels of antibodies to myelin basic protein in this mouse strain. High level of antibodies to myelin basic protein in pregnant females causes an increase in the blood level of these antibodies in the progeny. Inhibitory effect of antibodies to myelin basic protein on physical development, training process, and memory in mouse pups was detected.

Clinical, neurophysiological and immunological correlations in classical Rett syndrome.

Rett syndrome (RTT) is neurodevelopmental disorder with the onset at critical period of postnatal ontogenesis and age dependent occurrence of clinical manifestations. The aim of the present study was to investigate possible correlations of the age of disease onset with clinical manifestations at the stage 3 of illness and neurobiological parameters. The study was carried out in 38 girls with classical RTT, aged from 3 to 7 years, and twenty and eighteen patients with the disease onset before and after the age of one year were divided into the groups 1 and 2 (Gr1 and Gr2), respectively. Quantitative EEG (QEEG) and measurement of the serum levels of autoantibodies (AAB) to nerve growth factor (NGF) were performed. Clinically, speech and motor functions were significantly more severely affected in the Gr1 than in the Gr2. In QEEG, spectral density of theta activity was significantly higher in Gr1 than in the Gr2. The titer of AAB to NGF was significantly increased in comparison with healthy controls, and the titer in Gr2 was higher than in Gr1. The data obtained suggests that patients with the classical RTT can be divided into subgroups according to the age of disease onset and genetic factors such as mosaicism of MeCP2 mutation may be associated with the heterogeneity of phenotype in RTT patients.

Brain-directed autoantibodies levels in the serum of Rett syndrome patients.

Increased titer of brain-directed autoantibodies (AAB) may represent a risk for brain development in children with Rett syndrome (RTT). The aims of this work were to study the levels of brain-directed AAB, mainly nerve growth factor (NGF) and S-100 protein AAB, to analyze morphological features of brain labeling by AAB produced in RTT patients, and to correlate with clinical manifestation. The increased titer of anti-NGF AAB, but not of anti-S100 AAB has been determined in the blood of RTT patients. The blood from five RTT girls was investigated repeatedly (two to four times) within 0.5-3 years. In these RTT patients the level of anti-NGF AAB was stable, not depending on the stage of illness, so individual stability of anti-NGF AAB levels have been detected. However, the negative correlation between the level of these AAB and severity of disease has been found: girls with the milder course of illness (with relative preservation of speech and locomotor functions, later disease onset, and later development of regressive symptoms) were characterized by the higher levels of AAB. The study also revealed immunohistochemical labeling of neuronal population with serum from RTT patients. Serum AAB from RTT cases labeled the cytoplasm and apical dendrites of pyramidal neurons in the neocortex and hippocampus, neurons in basal ganglia and brain stem, but not in the cerebellum of rats. Our results show the presence of brain-directed AAB in blood serum of RTT patients, which suggests an autoimmune component in pathogenesis of RTT.

Intracellular alterations of the creatine kinase isoforms in brains of schizophrenic patients.

Postmortem brain tissues of schizophrenic patients were found to contain 5-10 times less water-soluble creatine kinase (BB CK) and 1.5-3 times less mitochondrial creatine kinase as compared to control. The major part of BB CK in schizophrenic brain tissues, contrary to control, was found to be insoluble in water (particulate form of BB CK) and could be extracted from brain tissue with strong denaturating agents. The particulate form of BB CK did not have any enzymatic activity but activity was found after the solubilization of this isoenzyme. The observed BB CK translocation into the particulate inactive form and the decrease of mitochondrial CK content to schizophrenic brains may reflect changes in the synthesis and the utilization of creatine phosphate.