Nejrohimiâ

The search for biological markers of neurodegenerative diseases, namely, Alzheimer’s (AD) and Parkinson’s (PD) diseases, is actual problem for fundamental biology and modern medicine. The aim of this review was to present some new results on biomarkers of these neurodegenerative disorders, mainly in biological fluids, like plasma and cerebrospinal fluid. Novel biomarkers in AD include plasma assays for amyloid-β and phosphorylated tau and PET (positron emission tomography) scans, which show great promise for clinical and research use. In PD research, serum cystatin C (Cst3) and homocystein in PD patients were higher than in serum of the normal control group and they were considered as new inflammatory biomarkers. Cst3 in biological fluids was suggested as a promising biomarker for diagnosing PD. Recently, extracellular vesicles (exosomes) have been reported as a new concept in the biomarker field. Serving as transfer vehicles between cells, they represent a promising source of biomarkers for a number of diseases, including neurodegenerative disorders. To date, developmental mechanisms and approaches to the treatment of neurodegenerative diseases (AD, PD) seemingly are extremely relevant, requiring common solutions and the development of new approaches.

Recent scientific studies indicate that angiogenesis and neurogenesis are interrelated processes that determine the functional outcome after ischemic stroke. This literature review presents current data on neurovascular interactions in ischemic stroke, describes the role of the family of vascular endothelial growth factors in the regulation of angiogenesis and neurogenesis, which play a leading role in neuronal survival and neuroplasticity. The authors searched the literature on the pathophysiological role of VEGF in acute cerebral ischemia using the relevant keywords into the PubMed and Google Scholar search engines, as well as Scopus, Web of Science, MedLine, The Cochrane Library, EMBASE, Global Health, CyberLeninka, eLibrary, and other databases. Clinical studies evaluating the role of VEGF in ischemic stroke are in most cases based on animal models, and their results are ambiguous, which is determined by the versatility of its action. VEGF is an important regulator of angiogenesis, neuroprotection and neurogenesis, but its negative effect has also been proven in the form of an increase in the permeability of the BBB and, as a consequence, cerebral edema, as well as the activation of inflammatory processes. Thus, further study of VEGF is needed to determine its role in functional recovery after ischemic stroke.

Extracellular vesicles are macromolecular complexes produced by virtually all types of eukaryotic and prokaryotic cells. According to modern concepts, they allow cells to exchange information, regulate each other’s activity and coordinate their actions during the complex processes of development, maintaining homeostasis, tissue regeneration, etc. Extracellular vesicles have a number of unique properties: the ability to accumulate certain types of proteins and nucleic acids, protect them from degradation and ensure their delivery to target cells, which can be used to create biomimetic approaches to the therapy of a wide range of diseases. The composition of vesicles, the preference for docking with a particular cell type, and ultimately their therapeutic potential are very flexible parameters and are highly dependent on the type and properties of the producer cell culture, as well as cultivation conditions. This review gives an idea of the state and prospects of the therapeutic strategies implied the application of extracellular vesicles for neuroprotection and stimulation of brain tissue regeneration after injury, and also considers existing clinical studies which use extracellular vesicles in the field of neurology and neurosurgery. Particular attention in the review is given to new promising approaches to increasing the production of extracellular vesicles, manipulating their contents, and increasing the efficiency of targeted docking in order to increase their therapeutic activity and specificity.

Polyneuropathies are a heterogeneous group of immune-mediated diseases, among which Guillain–Barré syndrome and chronic inflammatory demyelinating polyneuropathy are the most frequent. On the contrary, amyotrophic lateral sclerosis is most often considered as a disease, whose development is practically not associated with changes in the function of the immune system. This review summarizes the latest data on changes in the T-lymphocyte subpopulations and their function in the blood and cerebrospinal fluid in the aforementioned diseases. These data suggest that regulatory T cells and NKT cells may play an important role in the development of the discussed pathologies. We stress the necessity of accumulation and analysis of data on T-cell subpopulations, as well as the sequence of T-cell receptors, HLA, and CD1 in patients for the development of approaches to the diagnosis and possible therapy of these diseases.

Violation of neuroimmune regulatory interrelation, caused, in particular, by a change in the immune cell’s functional phenotype due to chronic ethanol intoxication, is an essential link in the pathogenesis of alcoholism. The unidirectional influence of most psychoactive drugs on the cells of the nervous and immune systems allows to consider immune cells as model objects for influencing intersystem functional interrelation. Based upon our own priority data on the presence of immunomodulatory properties in chronic alcohol intoxication at the original anticonvulsant acting on the molecular targets of ethanol influence in the central nervous system and the immune system, the aim of the present study was to evaluate the central effects of peripherally injected lymphocytes with in vitro modulated functional activity by a synthetic ligand of the GABAA-receptor complex meta-chlorobenzhydrylurea in long-term alcoholized animals. It was shown that transplantation of lymphocytes pre-cultivated with the anticonvulsant in syngeneic long-term alcoholic recipients achieves a decrease in alcohol motivation and stimulation of behavioral activity in the “open field” test. Editing of behavioral patterns characteristic for chronic alcohol intoxication was recorded against the background of a decrease in pathogenetically significant brain structures of pro-inflammatory cytokines IL-1β, IL-6, TNF-α, IFN-γ and an increase in the anti-inflammatory cytokine IL-10, as well as an increase in the level of BDNF in the hippocampus, which allows us to consider a decrease in neuroinflammation and stimulation neuroplasticity as possible mechanisms for editing the behavior of recipients. Visualization of functionally active lymphocytes pre-cultured with meta-chlorobenzydrylurea in the brain’s parenchyma of long-term alcoholized recipients also suggests a direct effect of injected lymphocytes on CNS cells. Thus, immune cells modulated in vitro with meta-chlorobenzydrylurea by relatively independent mechanisms have positive psychoneuromodulating effects in chronic ethanol intoxication, which makes it possible to consider adoptive immunotherapy as a promising method in the treatment of alcoholism.

Diabetic peripheral neuropathy (DPN) is the most common complication of diabetes mellitus type 2 (DM2) and is associated with significant morbidity and mortality. The pathophysiological mechanisms leading to the development of DPN have not been fully studied and are still debatable. Currently, immune-mediated mechanisms of its development are being discussed. The aim of this study was to estimate the content of TNF-α in the blood serum of patients with DM2 complicated by DPN and to assess the significance of this factor in the development and progression of DPN. An open comparative study was conducted with the participation of 83 patients with DM2 of different duration. In patients with clinical manifestations of DPN and long-term course of DM2 (group 2), the level of TNF-α was significantly higher compared to patients with DM2 and duration of DPN less than 2 years, and both studied groups of patients with DM2 and DPN had a high level of TNF-α in comparison with the control group. The results obtained indicate a more aggressive immune-mediated process that develops with a longer duration of DM2 and makes a negative contribution to the functioning of the peripheral nerve fiber.

Objective of the study – determination of quantitative characteristics of small extracellular vesicles (sEV) in the blood of patients with non-suicidal self-injury (NSSI) and comparison of the concentration and size of sEV’s in patients with major depressive disorder (MDD) with and without NSSI, as well as an assessment of the relationship between the sizes and concentrations of sEV in the sample with such parameters as the severity of situational and personal anxiety, depression and suicidal risk. The study included 28 patients (11 m./17 f.) with a current episode of major depression and at least five episodes of NSSI in the last 12 months (main group, mean age 28.3 years) and 28 patients with major depression identical in sex and age without NSSI throughout life (comparison group). Patient mental status was assessed using the MINI interview, the Beck Depression Inventory II (BDI II), and the Spielberger Anxiety Scale. Isolation of sEV from blood was carried out using polyethylene glycol (PEG) precipitation and gel filtration. The size and concentration of isolated particles were estimated using dynamic light scattering (DLS) and nanoparticle tracking analysis (ATN). The groups differed significantly in the severity of depression according to the BDI-II questionnaire, the Spielberger Situational Anxiety Scale, and the Spielberger Personality Anxiety Scale. The assessment of suicidal risk, carried out according to the corresponding module of the MINI questionnaire, revealed a significantly larger number of participants with medium and high suicidal risk in the group of patients with NSSI. The sEV fraction was isolated from the blood of the patients of the main group and the comparison group. There were no differences in the concentration and size of sEV between groups of patients with depression with and without NSSI. In our study, the dependence of the concentration and size of sEV on the severity of depression, situational and personal anxiety, and the severity of suicidal risk wasn’t revealed. Conclusion: NSSI in individuals with major depressive disorder is associated with a more severe course of the disorder (greater severity of depression, situational and personal anxiety), as well as a higher risk of suicide. Our study did not reveal any differences in the quantitative characteristics of sEV in patients with a depressive episode with and without NSSI. Future studies should focus on investigating the structural differences and functional features of sEV in NSSI.