The authors propose a novel approach to a comprehensive evaluation of neuroprotective effects using both in vitro and in vivo methods. This approach allows for the initial screening of numerous newly synthesized chemical compounds and substances from plant and animal sources while saving animal life by reducing the number of animals used in research. In vitro techniques, including mitochondrial suspensions and neuronal cell cultures, enable the assessment of neuroprotective activity, which can be challenging in intact organisms. The preliminary methods help outline the neuroprotection mechanism depending on the neurodestruction agent. The authors have validated a model of acute cerebrovascular accident, which simulates key cerebrovascular phenomena such as reduced cerebral blood flow, energy deficit, glutamate–calcium excitotoxicity, oxidative stress, and early gene expression. A significant advantage of this model is its ability to reproduce the clinical picture of cerebral ischemia: impaired motor activity; signs of neurological deficits (paresis, paralysis, etc.); as well as disturbances in attention, learning, and memory. Crucial to this approach is the selection of biochemical, molecular, and cellular markers to evaluate nerve tissue damage and characterize potential neuroprotective agents. Additionally, a comprehensive set of molecular, biochemical, histological, and immunohistochemical methods is proposed for evaluating neuroprotective effects and underlying mechanisms of potential pharmaceutical compounds.

Background. Chronic stress is the most common systemic factor that negatively affects the body's overall resistance, including wound healing. While many aspects of skin recovery after a surgical wound are well defined, the involvement of cells in the periwound rarea emains unsufficiently studied. Objective. To determine the morphological features of the periwound skin at different stages of the healing process after exposure to chronic social stress. Methods. Chronic social stress was modeled through long-term psychoemotional exposure in Wistar laboratory rats of the experimental group. Animals in both control and experimental groups were wounded in the interscapular area by skin excision. The material of the periwounds was collected on the 1st, 3rd, 7th, 14th and 30th days of wound healing and processed according to standard histological methods. Results. Exposure to chronic social stress led to thinning of the skin layers even before wounding. Visual wound healing was delayed. The main reparative processes by phases (inflammation, proliferation, and remodulation) also occurred with significant delays. Conclusions. Aggressive-dominant social stress is a rather strong damaging factor for susceptible animals, leading to impaired physiological skin regeneration. This was evident in the thinning of skin layers observed in histological samples even before wound application, resulting from reduced proliferation and differentiation processes. The negative consequences of chronic social stress were further manifested in the healing of a surgical wound: the repair processes during the main phases, in particular inflammation and proliferation, were delayed, which ultimately led to the chronicity of reparative regeneration.

Beta-blockers are first-line drugs in the treatment of chronic heart failure (CHF). However, there is no consensus on the specific effects of the beta-blockers of the I-III generation on energy metabolism in CHF. The aim of this study is to conduct a study of beta-blockers of different generations on myocardial energy metabolism in experimental CHF. CHF was modeled in white outbred rats by administering doxorubicin. The study drugs were administered intragastrically—new drug Hypertril (1-(β-phenylethyl)-4-amino-1,2,4-triazolium bromide)-3.5 mg/kg, Metoprolol—15 mg/kg, Nebivolol −10 mg/kg, Carvedilol 50 mg/kg, and Bisoprolol, 10 mg/kg. In the myocardium, the main indices of energy metabolism were determined—ATP, ADP, AMP, malate, lactate, pyruvate, succinate dehydrogenase (SDH) activity, and NAD-dependent malate dehydrogenase (NAD-MDH) activity. Traditional second-generation beta-blockers (Metoprolol and Bisoprolol) did not affect the studied indices of energy metabolism, and third-generation beta-blockers with additional properties—Carvedilol and, especially, Nebivalol and Hypertril—improved myocardial energy metabolism. The obtained results will help to expand our understanding of the effect of beta-blockers of various generations used to treat cardiovascular diseases on energy metabolism, and are also an experimental justification for the practical choice of these drugs in the complex therapy of CHF.

The authors propose a novel approach for a comprehensive evaluation of neuroprotective effects using both in vitro and in vivo methods. This approach allows for the initial screening of numerous newly synthesized chemical compounds and substances from plant and animal sources while preserving animal life. In vitro techniques, including mitochondrial suspensions and neuronal cell cultures, enable assessment of neuroprotective activity, which can be challenging in intact organisms. The preliminary methods help outline the neuroprotection mechanism depending on the neurodestruction agent. The authors have validated a model of acute cerebrovascular accident, which simulates key cerebrovascular phenomena such as reduced cerebral blood flow, energy deficit, glutamate-calcium excitotoxicity, oxidative stress, and early gene expression. A significant advantage of this model is its ability to reproduce the clinical picture of cerebral ischemia: impaired motor activity, signs of neurological deficits (paresis, paralysis, etc.), as well as disturbances in attention, learning, and memory. Crucial to this approach is the selection of biochemical, molecular, and cellular markers to evaluate nerve tissue damage and characterize potential neuroprotective agents. Additionally, a comprehensive set of molecular, biochemical, histological, and immunohistochemical methods is proposed for evaluating neuroprotective effects and underlying mechanisms of potential pharmaceutical compounds.

Restoration and strengthening of soft tissue structures of the musculoskeletal system underlie the principles of regenerative medicine to improve treatment results and prevent possible complications. Influencing various parts of the regenerative process, it is possible to correct the recovery time, the morphological properties of the scar, and, as a result, the clinical results of treatment. We have proposed using a polypropylene mesh (PM) impregnated with a metabolitotropic solution to restore damaged and strengthen weakened structures. The work aimed to study the effect of PM with metabolite impregnation on the regeneration process of soft tissues. A series of morphological and biochemical studies were carried out on laboratory animals. The degree of inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) mRNA expression was studied as indicators of tissue ischemia and their trophism in correlation with morphological changes in the zone of mesh implantation. Using a PM with a metabolitotrope increases the expression of eNOS mRNA by 10.8 times, and iNOS mRNA - reduces by 3.6 times. Morphologically coated PM causes a pronounced inflammatory effect, followed by a pronounced proliferation of connective tissue fibers around the mesh elements. Particular attention is drawn to the growth of the microvasculature and the increase in the number of anastomoses - 10.3% of the relative area compared to 8.8% in the group using PM without a metabolite. The metabolitotropic impregnation improves oxygenation and trophism of damaged soft tissues, which helps to stimulate regeneration.

Activation of sympathoadrenal and hypothalamic-pituitary systems under the influence of stress, accompanied by the release of neuromediators and neuropeptides, activation of mast cells producing cytokines, chemokines, etc., leads to the launch of a cascade of pathological processes which indicates that stress can lead to a violation of skin reparation. However, little is known about morphofunctional changes of skin cells under the influence of chronic social stress. The aim of this work was to assess changes in the number of mast cells in the rat skin after the influence of chronic social stress. The research was performed on 20 Wistar male rats aged 12-13 months, weighting 390 -430 g: 1st group – control (n = 10); modelled chronic social stress to the 2nd group (n = 10) by the 3-week social isolation and prolonged psycho-emotional impact. Stress was confirmed in an open field test. A skin flap sized 1*1 cm was excised on the back in the interscapular region on the day of wounding, and days 1, 3, 7, 14, 30 of wound healing. Mast cells were counted in wound surface area sections, selectively stained with toluidine blue. The wound healing process in the skin was characterized by a certain dynamic of mast cells’ number, as key cellular regulators of inflammatory and regenerative processes. In intact skin of the experimental group revealed a ten times exaggeration of mast cells compared to the control. In the control group, the content of mast cells gradually increased over the next 2 weeks and decreased to the initial level on the 30th day. Initial high level of mast cells decreased by 86,8% in experimental rats already on day 1 with a gradual rise in the next 2 weeks and raised by 593% compared to control group at day 30 which is associated with migration of immune-dependent cells as a result of partial removal of the stress response. Активація симпатоадреналової і гіпоталамо-гіпофізарної систем при стресі супроводжується вивільненням нейромедіаторів і нейропептидів, активацією тучних клітин, що продукують цитокіни, хемокіни та ін., призводить до запуску каскаду патологічних процесів, вказуючи, що стрес може призвести до порушення репарації шкіри. Однак у сучасних дослідженнях мало даних про морфофункціональні зміни клітин шкіри під впливом хронічного соціального стресу. Метою даної роботи була оцінка кількісних змін тучних клітин шкіри щурів після впливу хронічного соціального стресу. Дослідження проводили на 20 щурах-самцях лінії Вістар вагою 390 -430 г., віком 12-13 міс.: 1-а група – контроль (n=10); тваринам 2-ї групи (n=10) моделювали стрес 3-тижневою соціальною ізоляцією і тривалим психоемоційним впливом. Стрес підтверджено тестом на відкритому полі. Висікали шкірний клапоть розміром 1*1 см на спині в міжлопатковій ділянці в день нанесення рани і на 1, 3, 7, 14, 30 добу загоєння ран. Тучні клітини підраховували в зрізах взятих області ранової поверхні, селективно забарвлених толуїдиновим синім. Процес загоєння ран у шкірі характеризувався відповідними особливостями динаміки кількості тучних клітин, як регуляторів запальних та регенераторних процесів. В інтактних зразках експериментальної групи кількість тучних клітин була більшою в 10 р., ніж в контролі. Загальновідомі нормальні показники вмісту кількості тучних клітин у контрольній групі поступово збільшувались у наступні 2 тижні та зменшувались до вихідного рівня на 30 день загоєння ран. Початковий рівень тучних клітин у 2й групі знизився на 86,8% вже на 1 день з поступовим підйомом у наступні 2 тижні, проте він не досягав рівня контролю з подальшим підйомом на 593% порівняно з 1ю групою на 30 день, що пов’язано з міграційними процесами імунозалежних клітин як результат часткового зняття стресової реакції.