Bulletin of RSMU

ISSN Print 2500–1094 ISSN Online 2542–1204

Bulletin of RSMU

BIOMEDICAL JOURNAL OF PIROGOV UNIVERSITY (MOSCOW, RUSSIA)

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Priputnevich TV, Isaeva EL, Muravieva VV, Gordeev AB, Zubkov VV, Timofeeva LA, Mesyan MK, Shubina J, Makarov VV, Yudin SM

Currently, there are no criteria allowing to adequately assess composition and volume of the newborns' gut microbiota, which prevents early detection of the pathological processes and appropriate intervention. This study aimed to apply the methods of culturomics, proteomics and molecular genetic technologies to investigate the development of gut microbiota in healthy newborns delivered in the city of Moscow both vaginally and through a cesarean section. We examined 66 children, 33 of them delivered vaginally and 33 by cesarean section. The luminal bacterial flora samples were collected on the 1st, 7th and 30th days of life. There were 136 species of microorganisms belonging to 40 genera identified. We established that cesarean section slows down normal development of the gut microflora: through the follow-up period (1 month of life), gut microbiocenosis in such children did not yield the results on par with those registered in children born vaginally. Bifidobacteria were significantly more common in the vaginal delivery group: 84% of 109–1012 CFU/g versus 33% of 105–1012 CFU/g in the cesarean section group. At the same time, the former group had significantly less clostridia (33.3% and 65.4%, respectively) and lactose-negative Escherichia coli strains (2.4 and 19.4%, respectively) than the latter group.

Received: 2019-08-28

Published online: 2019-09-28

DOI: 10.24075/brsmu.2019.063

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VIEWS 4994

Fedotova EYu, Abramycheva NYu, Nuzhny EP, Ershova MV, Klyushnikov SA, Illarioshkin SN

Friedreich ataxia (FRDA) is the most common autosomal recessive ataxia associated with the non-coding GAA tandem repeats expansion in the FXN gene. Transcription impairment and frataxin protein deficiency are the key features of the disease pathogenesis. Our research was aimed to study the FXN gene mRNA expression as well as to carry out the clinical, genetic and epigenetic correlation analysis in a group of patients with homozygous expansion, in a group of their relatives with heterozygous expansion and in a control group. The FXN mRNA level was determined using the real-time polymerase chain reaction. Methylation pattern of CpG sites was evaluated by direct bisulfite sequencing. As a result of the study, the threshold values were obtained between the FRDA patients group, the group of heterozygous carriers and the control group (15 and 79%, respectively). The clinical and genetic features comparison with the FXN expression level revealed no significant correlation. When comparing gene expression with an epigenetic profile, it was found that hypermethylation of a number of CpG sites upstream of the trinucleotide repeats and some non-CpG sites downstream of the region of repeats inhibited expression. Thus, the identified methylated sites may be considered as a target for epigenome editing to increase the FXN transcription and, consequently, for target therapy of the disease.

Received: 2019-08-22

Published online: 2019-09-26

DOI: 10.24075/brsmu.2019.062

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VIEWS 4730

Fokin VF, Ponomareva NV, Konovalov RN, Krotenkova MV, Medvedev RB, Lagoda OV, Tanashyan MM

One of the methods of assessment of cognitive functions in patients with chronic ischemic cerebrovascular disease — CICD (dyscirculatory encephalopathy) implies studying connectivity of neural networks through the analysis of rest functional magnetic resonance imaging (rest fMRI) data. The main objective of this study was to assess the relationship between working memory (WM) characteristics and connectivity of various parts of the brain in patients diagnosed with CICD. The study involved 22 female CICD patients; they were divided into two groups, one with satisfactory level of WM and the other with compromised WM. We assessed intra-brain connectivity with the help of rest fMRI, using the SPM-12 and CONN18b software applications in Matlab platform. The other aspects evaluated were the gray to white matter ratio and the association of this indicator with WM. Significant differences in the intra-brain connectivity were registered in both the satisfactory WM group and the compromised WM group. The brain parts where those differences were found are left parahippocampal area and right supramarginal gyrus; right cerebellar hemisphere and left parietal, as well as left frontal areas; right cingular and left lingual gyri. In addition, we detected significant differences in the ratio in the gray and white matter volumes in both groups (p = 0.007). The results obtained indicate that memory deterioration in CICD patients is concomitant with deteriorating connectivity between the cortical areas, as well as between cerebellum and cortex, which may be associated with a more significant loss of the white matter.

Received: 2019-08-19

Published online: 2019-09-22

DOI: 10.24075/brsmu.2019.061

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VIEWS 4656

Berezhnoy DS, Fedorova TN, Kulikova OI, Stavrovskaya AV, Abaimov DA, Gushchina AS, Olshansky AS, Voronkov DN, Stvolinsky SL

The late stage of Parkinson’s disease is characterized by massive neuronal loss in the substantia nigra (SN) and degeneration of the dopaminergic innervation in the striatum. There is a need to assess the neuroprotective effect of antioxidants (AO) at this stage of the disease. The aim of our study was to assess the efficacy of two AO, carnosine and lipoic acid (LA), in the rat model of late-stage parkinsonism. The pathology was induced by a unilateral injection of 6-hydroxydopamine (6-OHDA) into the SN of the right brain hemisphere. AO were administered 4 times, starting on day 14 following the injection of the toxin. We investigated the effect of the injected drugs on the behavior of rats, the loss of neurons in the SN and the metabolism of biogenic neurotransmitter amines. Both AO dampened the development of 6-OHDA-induced neurological and behavioral symptoms. 6-OHDA induced a 90% drop (p = 0.01) in the levels of dopamine (DA) and its metabolites in the right striatum and caused death of over 95% of neurons (p = 0.01) in the SN of the right hemisphere (p = 0.01). AO did not have a significant effect on the number of neurons in the SN but caused an increase in the levels of DA metabolites, as compared to their levels in the animals exposed to 6-OHDA. Elevated DA (a 5.8-fold increase, p = 0.007) was observed only in the animals treated with carnosine. LA stimulated a 23% decline in serotonin levels (p = 0.06) and a 36% increase (p = 0.009) in its metabolite, 5-hydroxyindolacetic acid (5-HIAA). We conclude that although carnosine and LA did not have a direct neuroprotective effect, they could relieve the symptoms. This suggests that these AO could be used as an adjunctive component to antiparkinsonian therapy.

Received: 2019-08-12

Published online: 2019-09-18

DOI: 10.24075/brsmu.2019.060

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VIEWS 4512

Tanashyan MM, Medvedev RB, Lagoda OV, Berdnikovich ES, Skrylev SI, Gemdzhian EG, Krotenkova MV

Carotid artery stenosis is a risk factor for ischemic stroke. Surgical treatment is often used to improve cerebral perfusion and prevent the development of cerebrovascular pathology and related cognitive impairment. The aim of this prospective pilot study was to evaluate the cognitive functions (CF) of patients after surgery (open or endovascular intervention) on the internal carotid artery. The study included 90 patients (mean age 62 years, 71% of men) with atherosclerotic lesions of the carotid arteries. The CF was evaluated at four time points (before the intervention, 3, 6, and 9 months after) using cognitive scales and measuring cognitive evoked potentials. The state of the brain substance before and after the intervention was evaluated by the results of diffusion-weighted magnetic resonance imaging (DW-MRI). Three and six months after the operation, the patients demonstrated minor and varied CF alterations by the MMSE scale, but by the end of the observation period (9 months) the participants had their CF at the level close to that registered before the operation (p = 0.43). Thus, the intervention-associated changes in CF, regardless of the surgical approach, were primarily transient in nature. The rare cases of CF deterioration, as registered by the postoperative DW-MRI scans, were linked to the acute brain ischemia, both symptomatic and asymptomatic, and a perioperative stroke (1 case). Advanced age and altered cerebral arteries may be listed as the risk factors for the probable CF deterioration. Evaluation of the connections between CF alterations and multiple cases of intraoperative cerebral vascular embolism requires a longer observation period.

Received: 2019-08-15

Published online: 2019-09-17

DOI: 10.24075/brsmu.2019.059

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VIEWS 4762

Stavrovskaya AV, Voronkov DN, Kutukova KA, Ivanov MV, Gushchina AS, Illarioshkin SN

Parkinson’s disease (PD) is a common neurodegenerative disorder with a variety of motor and non-motor features. Non-motor symptoms, such as gastrointestinal dysfunction, usually set in 5 to 15 years earlier than motor manifestations. Cytoplasmic aggregates of phosphorylated α-synuclein are a typical marker of PD. They are observed not only in cerebral neurons but also in intramural plexuses of the intestine. Therefore, it is essential to investigate the peripheral component of the molecular pathogenesis of the disease using PD models, including those involving the use of parkinsonian neurotoxins, such as the well-known herbicide paraquat. The aim of this study was to identify a complex of early α-synuclein-related changes induced by long-term systemic administration of paraquat to rats at doses of 6 mg/kg. The open-field test revealed a decline in the motor activity of the experimental animals; the tapered beam walking test demonstrated a two-fold increase (р = 0.044) in the number of left paw slips. Besides, the intensity of staining for tyrosine hydroxylase (TH) in the substantia nigra and myenteric plexus fibers was 50% (р = 0.033) and 20% (р = 0.01) lower, respectively, in the main group than in the controls. Phosphorylated α-synuclein content was increased in the cell bodies of myenteric neurons and in TH-positive nervous fibers of the experimental animals. Changes indicating the development of peripheral α-synuclein pathology in the early stage of induced PD are similar to the changes observed in patients with PD at the onset of the disease. The proposed paraquat regimen could be very promising for PD modeling.

Received: 2019-08-12

Published online: 2019-09-14

DOI: 10.24075/brsmu.2019.058

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VIEWS 4865

Evdokimenko AN, Chechetkin AO, Druina LD, Tanashyan MM

Neovascularization of a carotid atherosclerotic plaque (AP) is associated with an increased risk of stroke. Contrast-enhanced ultrasonography (CEUS) is a widely used method for imaging intraplaque neovascularization in vivo. Unfortunately, there are no standardized guidelines for CEUS interpretation. The aim of this study was to identify the most reliable method for CEUS-based assessment of AP neovascularization. Seventy-eight AP were removed during carotid endarterectomy in 73 patients, of whom 5 had AP on both sides, and examined morphologically. All patients underwent preoperative duplex scanning and CEUS; Sonovue was used as a contrast agent. AP neovascularization was assessed on a 4-grade visual scale and with 3 different quantitative methods using QLAB software. On the visual scale (method 1), poorly (37%) and moderately (51%) vascularized plaques were the most common. Quantitative analysis (data were presented as Ме (Q1; Q3)) revealed that the number of blood vessels per 1 cm2 of the plaque (method 2) was 16 (10; 26), the ratio of the total vessel area to the plaque area (method 3) was 6% (3; 9), and AP ROI (method 4) was 2.6 dB (1.8; 4.1). Significant correlations were demonstrated between the results produced by method 2 and method 3 (р < 0.0001), method 3 and method 2 (р = 0.0006), and between pathomorphological findings and the results produced by methods 1–3, especially method 2 (р < 0.004). AP ROI brightness did not correlate with other results. The presence of hyperechoic components (calcifications) in AP dramatically reduced the reliability of US-based intraplaque neovascularization assessment. The most accurate CEUS-based quantitative method for assessing intraplaque neovascularization is estimation of blood vessel number per 1 cm2 of the plaque.

Received: 2019-08-15

Published online: 2019-08-31

DOI: 10.24075/brsmu.2019.057

Comments 0

VIEWS 4671

Khizhnikova AE, Klochkov AS, Kotov–Smolenskiy AM, Suponeva NA, Piradov MA

According to the literature data, only 5–20% of post-stroke patients are able to restore the hand motor function completely. Correct goal setting and individual approach to the patient's functional recovery are important. Our study aimed to develop an algorithm of impaired hand motor functioning assessment for post-stroke patients and to determine the principles of the rehabilitation tactics choosing based on the biomechanical analysis. Twenty five patients with hemispheric stroke and 10 healthy volunteers participated in the study. Formal clinical observation scales (Fugl–Meyer Assessment, Ashworth Scale, ARAT) and video motion analysis were used for evaluation of the hand motor function. Patients were divided into 2 groups according to the hand paresis severity (mild/moderate and pronounced/severe). Rehabilitation was carried out in both groups, including mechanotherapy, massage and physical therapy. It was revealed that in the 1st group of patients the motor function recovery in the paretic hand was due to movement performance recovery: biomechanical parameters restoration directly correlated with a decrease in the paresis degree according to the Fugl–Meyer Assessment Scale (r = 0.94; p = 0.01). In the 2nd group of patients, the motor function recovery in the paretic hand was due to motor deficit compensation: according to biomechanical analysis, the pathological motor synergies inversely correlated with a decrease in the paresis degree (r = –0.9; p = 0.03). As a result of the study, an algorithm for selecting the patient management tactics based on the baseline clinical indicators was developed.

Received: 2019-08-16

Published online: 2019-08-31

DOI: 10.24075/brsmu.2019.056

Comments 0

VIEWS 5298