Влияние предоперационного когнитивного расстройства на изменения электрической активности головного мозга у пациентов, перенесших одномоментное вмешательство на каротидных и коронарных артериях

HighlightsThe presence of preoperative mild cognitive impairment (MCI) in patients undergoing combined carotid endarterectomy and coronary artery bypass grafting is associated with an increased theta activity at the frontal and parieto-occipital regions of both hemispheres after surgery. AbstractAim. To study the impact of preoperative cognitive impairment on changes in electrical activity of the brain in patients undergoing combined carotid endarterectomy and coronary artery bypass grafting.Methods. Sixty-three patients undergoing combined carotid endarterectomy (CAE) and coronary artery bypass grafting (CABG) were included in the study. The patients were divided into three groups, depending on the preoperative cognitive functions: without cognitive impairment (n = 17), with MCI (n = 29), and with severe cognitive impairment (n = 17). High-resolution electroencephalography (EEG) (62 channels, bandpass filtered between 0.1–50.0 Hz, sampling rate of 1000 Hz) was performed 3–5 days before and 7–10 days after surgery.Results. Patients with severe cognitive impairment at baseline presented with higher theta activity at the frontal region of the left hemisphere compared to patients without cognitive impairment and patients with MCI (p = 0.048). At the same time, patients with MCI showed the most pronounced theta activity increase after surgery compared to preoperative levels at the frontal and parieto-occipital cortical regions of both the left and right hemispheres (p≤0.05). Postoperative changes of theta activity in patients with severe cognitive impairment were minimal and statistically insignificant.Conclusion. Patients without severe preoperative cognitive impairment presented with higher grade brain dysfunction in the form of increased theta activity at the frontal and parieto-occipital regions after combined CAE and CABG. A smaller decrease in theta power after surgery in patients with severe preoperative cognitive impairment, on the one hand, can indicate compensation after cerebral ischemia and resistance to hypoperfusion during on-pump cardiac surgery, and on the other, can be a manifestation of the ceiling effect and insufficiency of brain functional reserves.Основные положенияНаличие предоперационного умеренного когнитивного расстройства у пациентов, перенесших одномоментное вмешательство на каротидных и коронарных артериях, ассоциировано с выраженным послеоперационным увеличением тета-активности во фронтальных и парието-окципитальных отделах обоих полушарий. РезюмеЦель. Изучено влияние предоперационного когнитивного расстройства на изменения электрической активности головного мозга у больных, перенесших одномоментное вмешательство на каротидных и коронарных артериях.Материалы и методы. В исследовании участвовали 63 пациента, перенесших одномоментно каротидную эндартерэктомию и коронарное шунтирование с применением искусственного кровообращения. В зависимости от предоперационного состояния когнитивных функций участники разделены на три группы: без когнитивного расстройства (n = 17), с умеренным (n = 29) и тяжелым (n = 17) когнитивным расстройством. Электроэнцефалография высокого разрешения (62 канала, полоса пропускания 0,1–50,0 Гц, частота дискретизации 1 000 Гц) проведена за 3–5 дней и на 7–10-е сутки после вмешательства.Результаты. Установлено, что до операции у пациентов с тяжелым когнитивным расстройством показатели тета-активности во фронтальных отделах левого полушария были выше, чем у лиц без когнитивного расстройства и с умеренным когнитивным нарушением (p = 0,048). При этом после вмешательства у пациентов с умеренным когнитивным расстройством наблюдалось максимально выраженное увеличение тета-активности по сравнению с предоперационным уровнем во фронтальных и парието-окципитальных отделах коры левого и правого полушарий (p≤0,05). Тогда как у лиц с тяжелым когнитивным расстройством послеоперационные изменения тета-ритма были минимальны и не достигали статистической значимости.Заключение. Пациенты без тяжелых форм предоперационного когнитивного дефицита после одномоментного вмешательства на каротидных и коронарных артериях демонстрируют большую выраженность мозговой дисфункции по показателям тета-активности фронтальных и парието-окципитальных областей коры мозга. При этом меньшая выраженность изменений тета-ритма после операции у больных с тяжелым предоперационным когнитивным расстройством, с одной стороны, может быть индикатором компенсации хронической ишемии головного мозга и устойчивости к гипоперфузии при искусственном кровообращении, с другой – проявлением потолочного эффекта и недостаточности функциональных резервов

Changes in event-related synchronization/desynchronization of brain electric activity in cardiosurgical patients with postoperative cognitive dysfunction

Aim of the study was to analyze the event-related synchronization/desynchronization of brain electrical activity during visual selection task in patients underwent on-pump coronary artery bypass grafting (CABG) with and without postoperative cognitive dysfunction (POCD). Material and methods. The study included 32 men who underwent on-pump CABG, mean age 57,2 ± 6,08 years. All patients carried out extended neuropsychological testing, a multi-channel computer electroencephalography (EEG) 3-5 days before CABG and on the 7-10th day after the surgery. The POCD was determined according to the criterion: 20 % decrease in the cognitive indicator compared to that at baseline on 20 % of the tests included in the neuropsychological battery. Monopolar EEGs were recorded in 62 sites of 10-20 system with NEUVO encephalograph (Compumedics, USA) during cognitive task performing in patients with and without POCD. Statistical processing was performed using the STATISTICA 10.0. Results. It was found that the POCD patients had less pronounced theta desynchronization in the left frontal-central regions during the stage of 200-400 ms at the 7-10 days after CABG in comparison to patients without cognitive decline. Moreover, in the left parietal leads POCD patients had decreased theta desynchronization during the stage of 200-400 ms even before the surgery. At the 7-10 days after CABG, only the patients without POCD had a decrease of event-related theta activity in the left parietal leads compared with baseline. During the stage of 600-800 ms, the POCD patients had a lower degree of theta-desynchronization of both frontal-central and parietal regions of right hemisphere compared to patients without cognitive decline. Conclusion. The cognitive decline in patients after CABG determined according to neuropsychological testing is accompanied by pathological changes in the event-related theta activity. An analysis of event-related synchronization/desynchronization can be used both as predictor of postoperative cognitive impairment and as objective marker of POCD

Synthesis and functional characterization of 2-(2,5-dimethoxyphenyl)-N-(2-fluorobenzyl)ethanamine (25H-NBF) positional isomers

Serotonergic psychedelics, substances exerting their pharmacological action through activation of the serotonin 2A receptor (5-HT2AR), have continuously comprised a substantial fraction of the over 1000 reported New Psychoactive Substances (NPS) so far. Within this category, N-benzyl derived phenethylamines, such as NBOMes and NBFs, have shown to be of particular relevance. As these substances remain incompletely characterized, this study aimed at synthesizing positional isomers of 25H-NBF, with two methoxy groups placed on different positions of the phenyl group of the phenethylamine moiety. These isomers were then functionally characterized in an in vitro bioassay monitoring the recruitment of beta-arrestin 2 to the 5HT(2A)R through luminescent readout via the NanoBiT technology. The obtained results provide insight into the optimal substitution pattern of the phenyl group of the phenethylamine moiety of N-benzyl derived substances, a feature so far mostly explored in the phenethylamines underived at the N-position. In the employed bioassay, the most potent substances were 24H-NBF (EC50 value of 158 nM), 26H-NBF (397 nM), and 25H-NBF (448 nM), with 23H-NBF, 35H-NBF, and 34H-NBF yielding mu M EC50 values. A similar ranking was obtained for the compounds' efficacy: taking as a reference LSD (lysergic acid diethylamide), 24H-, 26H-, and 25H-NBF had an efficacy of 106-107%, followed by 23H-NBF (96.1%), 34H-NBF (75.2%), and 35H-NBF (58.9%). The stronger activity of 24H-, 25H-, and 26H-NBF emphasizes the important role of the methoxy group at position 2 of the phenethylamine moiety for the in vitro functionality of NBF substances

Serotonin 2A receptor (5-HT2AR) activation by 25H-NBOMe positional isomers : in vitro functional evaluation and molecular docking

Serotonergic psychedelics are defined as compounds having serotonin 2A receptor (5-HT2AR) activation as an important pharmacological mechanism. These compounds include the phenylalkylamine class, containing substances with e.g. 2C-X structures (phenethylamines) or their N-methoxybenzyl analogues (NBOMes). Besides their abuse potential, psychedelics are increasingly recognized for having therapeutic benefits. However, many psychedelics remain incompletely characterized, even concerning their structure-activity relationships. Here, five positional isomers of 25H-NBOMe, with two methoxy groups on the different positions of the phenyl ring of the phenethylamine moiety, were subjected to split-nanoluciferase assays assessing the in vitro recruitment of cytosolic proteins to the 5-HT2AR. Furthermore, molecular docking at the 5-HT2AR allowed estimation of which residues interact with the specific isomers' methoxy groups. Although the optimal substitution pattern of N-unsubstituted phenylalkylamines has been extensively studied, this is the first comparative evaluation of the functional effects of the positioning of the methoxy groups in the phenethylamine moiety of NBOMes

The Effect of Volatile Organic Compounds on Different Organisms: Agrobacteria, Plants and Insects

Bacteria and fungi emit a huge variety of volatile organic compounds (VOCs) that can provide a valuable arsenal for practical use. However, the biological activities and functions of the VOCs are poorly understood. This work aimed to study the action of individual VOCs on the bacteria Agrobacterium tumefaciens, Arabidopsis thaliana plants, and fruit flies Drosophila melanogaster. VOCs used in the work included ketones, alcohols, and terpenes. The potent inhibitory effect on the growth of A. tumefaciens was shown for 2-octanone and isoamyl alcohol. Terpenes (−)-limonene and (+)-α-pinene practically did not act on bacteria, even at high doses (up to 400 µmol). 2-Butanone and 2-pentanone increased the biomass of A. thaliana at doses of 200–400 μmol by 1.5–2 times; 2-octanone had the same effect at 10 μmol and decreased plant biomass at higher doses. Isoamyl alcohol and 2-phenylethanol suppressed plant biomass several times at doses of 50–100 μmol. Plant seed germination was most strongly suppressed by isoamyl alcohol and 2-phenylethanol. The substantial killing effect (at low doses) on D. melanogaster was exerted by the terpenes and the ketones 2-octanone and 2-pentanone. The obtained data showed new information about the biological activities of VOCs in relation to organisms belonging to different kingdoms

Acute behavioral and Neurochemical Effects of Novel N-Benzyl-2-Phenylethylamine Derivatives in Adult Zebrafish

Hallucinogenic drugs potently affect brain and behavior and have also recently emerged as potentially promising agents in pharmacotherapy. Complementing laboratory rodents, the zebrafish (Danio rerio) is a powerful animal model organism for screening neuroactive drugs, including hallucinogens. Here, we test a battery of ten novel N-benzyl-2-phenylethylamine (NBPEA) derivatives with the 2,4- and 3,4-dimethoxy substitutions in the phenethylamine moiety and the -OCH3, -OCF3, -F, -Cl, and -Br substitutions in the ortho position of the phenyl ring of the N-benzyl moiety, assessing their acute behavioral and neurochemical effects in the adult zebrafish. Overall, substitutions in the Overall, substitutions in the N-benzyl moiety modulate locomotion, and substitutions in the phenethylamine moiety alter zebrafish anxiety-like behavior, also affecting the brain serotonin and/or dopamine turnover. The 24H-NBOMe(F) and 34H-NBOMe(F) treatment also reduced zebrafish despair-like behavior. Computational analyses of zebrafish behavioral data by artificial intelligence identified several distinct clusters for these agents, including anxiogenic/hypolocomotor (24H-NBF, 24H-NBOMe, and 34H-NBF), behaviorally inert (34H-NBBr, 34H-NBCl, and 34H-NBOMe), anxiogenic/hallucinogenic-like (24H-NBBr, 24H-NBCl, and 24H-NBOMe(F)), and anxiolytic/hallucinogenic-like (34H-NBOMe(F)) drugs. Our computational analyses also revealed phenotypic similarity of the behavioral activity of some NBPEAs to that of selected conventional serotonergic and antiglutamatergic hallucinogens. In silico functional molecular activity modeling further supported the overlap of the drug targets for NBPEAs tested here and the conventional serotonergic and antiglutamatergic hallucinogens. Overall, these findings suggest potent neuroactive properties of several novel synthetic NBPEAs, detected in a sensitive in vivo vertebrate model system, the zebrafish, raising the possibility of their potential clinical use and abuse