Vol 21, No 2 (2021)

The review summarizes current data on the role of neuroinflammation and mast cells in the pathogenesis of nervous and mental diseases, such as multiple sclerosis, Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, depression, autism, migraine, schizophrenia and some others. The contribution of neuroinflammation to the pathogenesis of many of these diseases has been demonstrated. The involvement of mast cells in the development of the neuroinflammatory process has with varying degrees of evidence been shown for multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer’s disease and migraine. There is still no convincing evidence that mast cells contribute to neuroinflammation in Parkinson’s disease, depression, schizophrenia and autism spectrum disorder, although it is possible that they play a role in the pathogenesis of these diseases. Data on the causal role of neuroinflammation and mast cells in the development of neuropsychiatric diseases may become the basis for the development of new approaches to their pharmacological treatment. The review provides data on the first clinical trials of anti-inflammatory and mast cell activity-modulating drugs for the treatment of migraine, Alzheimer’s disease, multiple sclerosis and amyotrophic lateral sclerosis.

The review is devoted to inhibition of the complement anaphylatoxin activities in diseases of the central nervous system. Here we present epidemiological data on the prevalence of cerebrovascular diseases, in particular, ischemic stroke and craniocerebral trauma. The mechanisms of complement activation and complement-mediated pathology in the central nervous system are considered in detail. Clinical data confirming the role of the complement system in the pathogenesis of stroke and of post-traumatic brain injury are presented. We also summarize the results of in vivo specific activity studies of the complement anaphylatoxin inhibitors using animal models of stroke and traumatic brain injury. Briefly described is the present state of the art in developing drugs that target the effector compounds of the complement cascade.

BACKGROUND: In recent years, a significant increase in cerebrovascular pathology, which is often accompanied by cognitive deficits, has been noted all over the world.

AIM: The aim of this study is to determine the severity and structure of cognitive disorders depending on the level of 25(OH)D in patients with cerebrovascular disease.

MATERIALS AND METHODS: 146 patients with cerebrovascular disease aged from 30 to 80 years were examined. The comparison group consisted of 40 patients, comparable in age and gender, without the studied pathology. During the study, the level of 25(OH)D, interleukin-6, highly sensitive C-reactive protein in the peripheral blood was determined in patients and a neuropsychological examination was performed.

RESULTS: In patients with cerebrovascular disease, the level of 25(OH)D it was lower in comparison with patients without this pathology. Patients with higher rates of inflammatory factors had significantly lower concentrations of 25(OH)D in the peripheral blood. The study revealed a correlation between the level of 25(OH)D in peripheral blood and the results of neuropsychological testing: direct — MMSE, MoCA, FAB and reverse — Schulte tables (performance). When assessing cognitive disorders in patients with cerebrovascular disease, according to the results of neuropsychological testing, it was possible to identify significantly significant differences between the main and the comparison group according to the following scales: MMSE (p = 0.04), MoCA (p = 0.001), FAB (p = 0.007), Schulte Tables (performance) (p = 0.06), respectively. When interpreting the MMSE scale, significantly significant differences between the groups were found in the attention assessment (p = 0.03), and in the analysis of the MoCA scale — in the sections delayed reproduction (p = 0.03) and conceptualization (p = 0.04), respectively. In patients with cerebrovascular disease, memory is most affected by the type of delayed reproduction failure, which was observed in 53-76% of cases in our study.

CONCLUSIONS: The study found that the higher the concentration of 25(OH)D and the lower the level of interleukin-6 and highly sensitive CRP in the peripheral blood, the less likely it is to develop cognitive disorders. In patients with cerebrovascular disease, memory is most affected by the type of delayed reproduction failure.

BACKGROUND: Myeloperoxidase (MPO), the enzyme of leukocytes, catalyzes the production of reactive halogen species, which can modify the structure of lipoproteins. Chlorination and nitration of tyrosine residues in apolipoprotein A-1 lead to the formation of dysfunctional high-density lipoproteins (HDL-p), thus blocking the reverse cholesterol transport. Low level of high-density lipoprotein cholesterol (HDL-C) is associated with exacerbation of coronary heart disease, but the prognostic value of this index is not fully assessed.

AIM: The aim of this study was to examine a possible contribution of MPO to the atherosclerotic plaque development (the stable growth or the erosion and rupture) via the modification of HDL-p. That is to say we investigated the diagnostic values of measuring the total MPO (MPO-T), the active MPO (MPO-A) and the MPO/HDL-С relation in patients with hypertension and various forms of chronic coronary heart disease.

MATERIALS AND METHODS: The cohort under study included 44 patients with arterial hypertension and chronic coronary heart disease. All patients were divided into three groups according to the diagnosis: arterial hypertension without coronary heart disease (Group I, n = 20); arterial hypertension and the initially stable chronic coronary heart disease without acute complications in the anamnesis (Group II, n = 14); arterial hypertension and myocardial infarction (acute coronary syndrome) in the anamnesis (Group III, n = 10). The enzyme-linked immunosorbent assay (ELISA) for MPO-T and specific immuno-extraction followed by enzymatic detection (SIEFED) by fluorogenic substrate for MPO-A were applied. After that the ratio MPO-T/HDL-C or MPO-A/HDL-C was calculated.

RESULTS: The MPO-A and MPO-A/HDL-C ratio were significantly increased in the group III of patients with old myocardial infarction as compared with the patients of group II who had the initially stable coronary heart disease (p = 0.009 and p = 0.003, respectively). Besides, the level of HDL-C in the group III was significantly reduced (p = 0.013). Our measurements revealed the negative correlation between MPO-A and HDL-C concentrations (r = –0.31; p < 0.05), which is in line with the presumption of the study accomplished. Surprisingly, the correlation between MPO-T/HDL-C ratio and that MPO-A/HDL-C was stronger (r = 0.72; p < 0.05), than between MPO-T and MPO-A (r = 0.36; p < 0.05).

CONCLUSIONS: Our study demonstrates the importance of assessing MPO-T and MPO-A plasma concentrations and of calculating the ratio MPO/HDL-C as promising biomarkers in the complicated cases of chronic coronary heart disease. MPO-A and MPO-A/HDL-C values were elevated in the patients with old myocardial infarction, while the concentration of HDL-C remained decreased upon the transition from the acute to chronic phase of the disease.

BACKGROUND: The study of the mechanisms of interaction of paired structures of the mammalian brain is a fundamental problem of modern neuroscience, which is of great applied importance. Even mild underdevelopment of the corpus callosum in humans can lead to autism. It is known that the intensity of intraspecific interactions in BALB/c mice is lower than in white outbred ones, while some BALB/c substrains are characterized by underdevelopment of the corpus callosum.

AIM: To compare the morphological parameters of the large brain commissures in white outbred mice and BALB/c mice grown in the Rappolovo nursery (Leningrad region).

MATERIALS AND METHODS: The morphology of the corpus callosum was studied in 13 male white outbred mice and 7 male BALB/c mice at the age of 8 months.

RESULTS: In mice of both subpopulations, the area of the anterior commissure of the left hemisphere was smaller than that of the right hemisphere (p < 0.05). There were no differences between subpopulations in this parameter. The area of the left section of the corpus callosum trunkus in outbred mice was larger than the right one (p < 0.001), while in BALB/c mice the areas of the left and right slices did not differ. Despite the absence of significant differences in the area of the anterior part (rostrum et genu) of the corpus callosum the density of the location of oligodendrocytes in this brain structure in the mice of the two subpopulations was different. The number of oligodendrocytes in 0.01 mm² on the left section of the anterior part of the corpus callosum in BALB/c mice was greater than in white outbred mice (p < 0.05). A similar trend was revealed when comparing slices of the right hemisphere (p = 0.065).

CONCLUSIONS: The large area of the right parasagittal slice of the anterior commissure suggests that some of its constituent fibers do not cross the midline, but end within the same hemisphere, which may be the morphological basis for the functional dominance of the temporal cortex of the left hemisphere in mice of both subpopulations. The corpus callosum in BALB/c mice is developed symmetrically, and in white outbred ones – asymmetrically. This feature may be the morphological basis for the functional dominance of the parietal cortex of the right hemisphere in outbred animals.

BACKGROUND: Given the recently proposed role of the rare galanin receptor-2 (GALR2) gene’s missense mutation (SNP rs61745847) in the etiology of MS, we genotyped rs61745847 in a group of MS patients that was enriched with an unfavorable disease course cases.

MATERIALS AND METHODS: Our study cohort consisted of 100 MS patients selected based on their progressive course, high disease progression rate and pediatric onset. To determine the nucleotide sequence of GALR2 gene fragment, surrounding the rs61745847 area, Sanger sequencing of PCR amplicons was performed.

RESULTS: No homozygous rs61745847 carrier was found in our cohort, and the region of exon 2 surrounding rs61745847 completely coincided with the reference sequence (Gene Bank NC_000017.11). In agreement with previously published data on Canadian and Brazilian populations of patients, our study of a Russian cohort confirmed the rarity of the rs61745847 variant, including among patients with rapidly progressive MS.

CONCLUSIONS: Thus, although structural changes in the GALR2 gene associated with rs61745847 may play a significant role in individual patients carrying this rare mutation, it is unlikely that such changes determine an unfavorable disease course of MS in general.