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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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 3828

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 4029

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 4105

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

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VIEWS 3976

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

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VIEWS 4406

Mettini E, Yasko BA, Kazarin BV, Ostroushko MG

Sometimes, a minor scientific event leaves a much more memorable trace than a large conference. On May 30–31, 2019, Pirogov Russian National Research Medical University hosted a symposium on medical identities in various communities. Reports, reviews and discussions presented at the symposium focused on the problem of identity, a unique phenomenon that results from self-reflecting on a complex dynamic process of personal development. Professional identity is particularly important for a medical doctor. This article inspired by the reports of our colleagues summarizes the results of the symposium.

Received: 2019-08-06

Published online: 2019-08-26

DOI: 10.24075/brsmu.2019.055

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VIEWS 3513

Kremneva EI, Akhmetzyanov BM, Dobrynina LA, Krotenkova MV

Hemodynamic parameters of blood and cerebrospinal fluid (CSF) flow can be measured in vivo using phase-contrast MRI (PC-MRI). This opens new horizons for studying the mechanisms implicated in the development and progression of age-related cerebral small vessel disease (SVD). In this paper, we analyze associations between cerebral arterial, venous and CSF flow impairments and SVD features visible on MRI. The study was carried out in 96 patients with SVD (aged 60.91 ± 6.57 years) and 23 healthy volunteers (59.13 ± 6.56 years). The protocol of the MRI examination included routine MRI sequences (T2, FLAIR, T1, SWI, and DWI) applied to assess the severity of brain damage according to STRIVE advisory standards and PC-MRI used to quantify blood flow in the major arteries and veins of the neck, the straight and upper sagittal sinuses, and CSF flow at the aqueduct level. We analyzed the associations between linear and volumetric parameters of blood/CSF flow and the degree of brain matter damage using the Fazekas scale. We observed a reduction in tABF, stVBF, sssVBF, aqLF, Saq, and ICC values and a rise in Pi associated with WMH progression, as well as a gradual decline in tABF and an increase in Pi, Saq and ICC associated with a growing number of lacunes (р < 0.05). Patients with early (< 5) MB had lower sssVBF and stVBF rates in comparison with patients without MB; aqLF, Saq, and ICC values were elevated in patients with 5 to 10 MB, as compared to patients without MB or early (< 5) MB. The established associations between MRI findings in patients with SVD and blood/CSF flow impairments suggest the important role of mechanisms implicated in the disruption of Monro–Kellie intracranial homeostasis in promoting SVD.

Received: 2019-07-28

Published online: 2019-08-25

DOI: 10.24075/brsmu.2019.054

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VIEWS 4180

Lychagin AV, Garkavi AV, Islaieh OI, Katunyan PI, Bobrov DS, Yavlieva RH, Tselisheva EYu

Osteoarthritis (OA) affects both elderly people, for whom it is one of the main causes of disability, and people of active working age and is an urgent clinical and social problem of resistance of pain syndrome to therapy. The disease is characterized by both destruction of intra-articular and paraarticular structures, such as subchondral bone. While OA is an important sign of pathological changes believe the bone marrow edema (BME). This work examines the effect of BME on development osteoarthritis, and therapeutic approaches to the management of patients with OA. The aim of the study was to develop a method of treatment of BME in OA of the knee joint by locally intraosseous injection of autologous thrombotic-rich plasma (PRP) into the edema zone. In this study 17 patients with the diagnosis: Osteoarthritis II-IV Grade. according to the classification of Kellgren–Lawrence, in which areas of local inflammation in the form of BME were detected on MRI in the subchondral zone in accordance with the international classification of WORMS (Whole Organ Magnetic Resonance Imaging Score). The mean age of patients was 41,7 ± 14,3 years, 10 of them were women and 7 men. Patients were treated with autological platelet-rich plasma under x-ray control injected from extra-articular intraosseous access in the area of BME. Evaluation of effectiveness of treatment performed by VAS, WOMAC and KOOS scales, before the introduction of autoplasma, after 1 and 3 months after the start of treatment. Three months after the manipulation, there was a statistically significant decrease in the intensity of inflammatory syndrome: for WOMAC by 17.5%, for KOOS by 19.4% and for VAS by 33,1% (p < 0,01). Thus, the efficiency of intraosseous Infiltration of autologous platelet-rich plasma in the treatment of patients with OA, accompanied by edema of the bone marrow in the subchondral zone, was proved.

Received: 2019-07-12

Published online: 2019-08-20

DOI: 10.24075/brsmu.2019.053

Comments 0

VIEWS 4332