ENDOTHELIAL DYSFUNCTION UNDER EXPERIMENTAL SUBARACHNOID HEMORRHAGE. POSSIBLE WAYS OF PHARMACOCORRECTION

Purpose of the article: to study the effect of acelysine and nimodipine on certain endothelial dysfunction indicators and to evaluate their therapeutic efficacy after subarachnoid hemorrhage in rats. Materials and Methods: an experimental study was carried out using 50 Wistar rats of both sexes. Spontaneous subarachnoid hemorrhage was modeled in animals. Three groups of animals were identified: a control group, a group of animals received a standard therapeutic dose of acelysine, and a group received a standard therapeutic dose of nimotop. Each group included 15 animals. There were also 5 intact animals. The animals were withdrawn from the experiment on days 4 and 7 after the motor and exploratory activity determination. Motor and exploratory activity determination was carried out following SAH with the “Open Field” technique. Determination of biochemical markers of endothelial dysfunction was performed in a rat brain homogenate. Results and discussion. It was found that modeling of subarachnoid hemorrhage (SAH) led to the oxidative stress development development and the product of oxidative modification of proteins (nitrotyrosine (Ntz) on the 4th and especially on the 7th day of the experiment) increase in the brain tissues. Starting from the 4th day, we registered a compensatory increase in the activity of NO-synthase (NOS) - by 56%, followed by a decrease in its activity on the 7th day, by more than 33% against the intact group of animals. It was registered a compensatory increase in VEGF-A in rats with SAH modeling on the 4th day of the experiment and its further decrease on the 7th day. The established pathobiochemical changes in the brain tissue were accompanied by the cognitive deficit development in experimental animals, especially on the 7th day of the SAH. SAH led to a significant decrease in the total activity of animals by 2.63 times, a decrease in the distance traveled by animals by 1.89 times, the number of freezes increased by 1.86 times and the immobility of animals increased when moving from the periphery to the center and immobility in the center of the arena (anxiety, fear, disorientation), as well as a decrease in the distance traveled and the speed of movement in illuminated center of the arena 2 and 2.6 times, respectively. Experimental therapy with acelysine 15 mg/kg led to the normalization of biochemical indicators of endothelial dysfunction: concentration of nitrotyrosine, starting from the 4th day of the experiment, increased eNOS activity and VEGF-A concentration (by 75% and 64% on 7th day). The administration of namidopine led to less pronounced effects, statistically significant changes occurred only in relation to the VEGF-A concentration. Administration of namidopine resulted in only a slight increase in VEGF-A concentration. Acelysine and nimotope significantly increased the total activity of rats on the 7th day after SAH by 76.3% and 48.8%, respectively. In animals treated with acelysine, anxiety and fear decreased. The animals were less aggressive and more empathic - long-term grooming increased 3 times. The administration of nimotop in rats survived SAH had a less pronounced positive effect on behavior. Nimotop did not effect on indicators of general activity and did not increase the total distance traveled. Animals received nimtop were inactive by the 7th day of treatment. Conclusions: Experimental therapy with acelysine led to the normalization of biochemical parameters of endothelial dysfunction, namely nitrotyrosine concentration, starting from the 4th day of the experiment and increased eNOS activity and VEGF-A concentration. It should be noted that, in contrast to the rats of the control group, under prescription of acelysine, there was an increase in the concentration of eNOS and VEGF-A both on the 4th and 7th days of the experiment. The administration of namidopine led to less pronounced effects, statistically significant changes occurred only in relation to the VEGF-A concentration. The administration of acelysin to animals after SAH had a beneficial effect on the emotional status and behavior of animals, and also led to the normalization of their general activity and orientation-exploratory activity. The mechanism of edotheliotropic effect of acelysine, in our opinion, is associated with its antioxidant effects, modulating impact on endothelial NOS, as well as its property, indirectly, to influence on increase VEGF content. Nimotope therapy had no effect on the emotional status and behavior of the animals. The use of calcium channel blockers revealed such side effects as depression, drowsiness, diplopia, and disorientation

Exploring Refinement Strategies for Single Housing of Male C57BL/6JRj Mice: Effect of Cage Divider on Stress-Related Behavior and Hypothalamic-Pituitary-Adrenal-Axis Activity

Introduction: Single housing of laboratory mice is a common practice to meet experimental needs, or to avoid intermale aggression. However, single housing is considered to negatively affect animal welfare and may compromise the scientific validity of experiments. The aim of this study was to investigate whether the use of a cage with a cage divider, which avoids physical contact between mice while maintaining sensory contact, may be a potential refinement strategy for experiments in which group housing of mice is not possible.Methods: Eight-week-old male C57BL/6JRj mice were single housed, pair housed or pair housed with a cage divider for four (experiment 1) or ten (experiment 2) weeks, after which we performed an open field test, Y-maze spontaneous alternation test, elevated plus maze test, an auditory fear conditioning task, and assessed responsiveness of the hypothalamic-pituitary-adrenal (HPA) axis.Results: Housing conditions did not affect body weight, exploratory activity, anxiety, working memory, fear memory processing or markers for HPA-axis functioning in either experiment 1 or experiment 2. There was an increased distance traveled in mice housed with a cage divider compared to pair housed mice after 4 weeks, and after 10 weeks mice housed with a cage divider made significantly more arm entries in the Y-maze spontaneous alternation test.Conclusion: Taken together, our study did not provide evidence for robust differences in exploratory activity, anxiety, working memory and fear memory processing in male C57BL/6JRj mice that were single housed, pair housed or pair housed with a cage divider.

Modeling Functional Limitations, Gait Impairments, and Muscle Pathology in Alzheimer’s Disease: Studies in the 3xTg-AD Mice

Gait impairments in Alzheimer’s disease (AD) result from structural and functional deficiencies that generate limitations in the performance of activities and restrictions in individual’s biopsychosocial participation. In a translational way, we have used the conceptual framework proposed by the International Classification of Disability and Health Functioning (ICF) to classify and describe the functioning and disability on gait and exploratory activity in the 3xTg-AD animal model. We developed a behavioral observation method that allows us to differentiate qualitative parameters of psychomotor performance in animals’ gait, similar to the behavioral patterns observed in humans. The functional psychomotor evaluation allows measuring various dimensions of gait and exploratory activity at different stages of disease progression in dichotomy with aging. We included male 3xTg-AD mice and their non-transgenic counterpart (NTg) of 6, 12, and 16 months of age (n = 45). Here, we present the preliminary results. The 3xTg-AD mice show more significant functional impairment in gait and exploratory activity quantitative variables. The presence of movement limitations and muscle weakness mark the functional decline related to the disease severity stages that intensify with increasing age. Motor performance in 3xTg-AD is accompanied by a series of bizarre behaviors that interfere with the trajectory, which allows us to infer poor neurological control. Additionally, signs of physical frailty accompany the functional deterioration of these animals. The use of the ICF as a conceptual framework allows the functional status to be described, facilitating its interpretation and application in the rehabilitation of people with AD.

Behaviour and animal welfare indicators of broiler chickens housed in an enriched environment

The present study aimed to assess the influence of adding straw bales, step platforms, and laser projectors as environmental enrichment resources on the behaviour and welfare indicators of broiler chickens (Gallus gallus domesticus). A sample of 4,000 day-old male Cobb® 500 birds was used. The experimental treatments consisted of No Environmental Enrichment (NEE)—similar to a conventional environment; and Environmental Enrichment (EE)—environment enriched with straw bales, step platforms, and laser projectors, with four replicates per treatment of 500 animals. Behavioural characteristics (ethological observation through cameras, grab test, and modified touch test) and animal welfare indicators (pododermatitis and dorsal cranial myopathy) were assessed. The birds submitted to the EE treatment exhibited greater exploratory activity and expression of behaviours associated with comfort and welfare, whereas those in the NEE group were less active. Locomotion and play fighting behaviour decreased and behaviours associated with comfort increased as age advanced. The frequencies of interaction with laser spots and birds lying around straw bales were the highest in the 1st week (P<0.01). The behaviours of pecking at straw bales (P<0.0004), using the step platforms (P = 0.0001) and being on top of straw bales (P<0.0002) gradually increased. The chickens accessed the feeding troughs the most in the period of 0800 hours (P<0.0001) and expressed the highest frequencies of behaviours associated with comfort in the 1400 hours and 1700 hours periods. The birds in the EE group were calmer in face of human presence and touch and scored higher in animal welfare indicators. Adding straw bales, step platforms, and laser projectors increased locomotion, reduced expression of fear, and improved animal welfare indicators of broiler chickens.

Trade Journals' Research Chops

The problem of choosing the leading journals has become especially relevant due to increased number of issuable magazines. The following chapter offers identification and analysis of academic trade journals, defines the leading Russian journals on economics. The application of research chops in evaluation of academic and teaching staff's exploratory activity is of particular significance. Obtained results can be taken into account by scientific institutions for the purpose of determining strategic priority of the journals' development.

Behavioral and Brain Structural Changes in Kindled Rats Induced by Coriaria Lactone/Pentylenetetrazol

Epilepsy is a common chronic neurological disease that is characterized by spontaneous seizures. It is commonly comorbid with behavioral and mood disorders. No studies have yet examined the behavioral or structural brain changes associated with coriaria lactone (CL)-induced and pentylenetetrazol (PTZ)-induced kindlings. This study examined whether the increased seizure susceptibility induced by CL/PTZ is accompanied by behavioral impairments and aimed to identify associated structural brain changes. Kindling models were induced using CL and PTZ, with 10 rats in each group. After successful kindling, rats were subjected to brain structural imaging using T2-weighted imaging and underwent behavioral tests, namely, the open field test, water maze tasks, and contextual fear conditioning. Voxel-based morphometry was then used to identify possible brain structural changes associated with kindling and/or behaviors. Support-vector machine learning was also applied for the integrative analysis of behavioral changes and structural brain imaging. In the open field test, both the CL (P = 0.04) and PTZ groups (P = 0.002) spent more time in the central area than the control group. Only the PTZ group (50.29 ± 29.56 s) showed a freezing time that was significantly less than that of the control group (94.8 ± 41.04 s; P = 0.024, Tukey's HSD-corrected) in contextual fear conditioning, which is suggestive of impaired fear-associated learning ability. Furthermore, brain imaging analysis revealed that the gray matter volume (GMV) of the hippocampus changed in both the CL and PTZ groups when compared to control. The support-vector machine learning model indicated that the retrosplenial dysgranular and primary somatosensory cortices were associated with both of the mentioned kindling models. Furthermore, the support-vector regression model results indicated that kindling-associated GMV changes can be used to predict general exploratory activity in the open field test. In conclusion, this is the first study to report greater general exploratory activity in a CL-induced kindling model. Moreover, the general exploratory activity in the open field test can be predicted by the GMV of brain regions associated with kindling.

Amateurs’ Exploration of Wine: A Pragmatic Study of Taste

Amateurs are neither regular consumers nor professionals. What makes them distinctive? To answer that question, this ethnographic study focuses on wine amateurs who show a distinctive feature compared to regular consumers: for them, wine is not a straightforward reality but a world to explore. Wine exploration drives an evolution that transforms both wine and amateurs’ disposition towards it. Amateurs usually start with the discovery of the wines and their tastes, which may turn into an ability to attune to and finally produce taste and good quality. Amateurs’ passion, initially fuelled by the discovery of unknown tastes, is then informed by the renewal of the taste experience itself. Following amateurs in their exploratory activity allows us to extend the analysis beyond scholars’ usual focus on one of its particularly normative stages, and to propose a renewed account of the amateur that is quite remote from the standard image of the ‘cultural prescriber’.