Pericellular Edema Research Articles

Effect of Sertraline and Vortioxetine on Stress-Induced Brain Injury in Rats: Biochemical and Histopathological Evaluations

Objectives Our aim was to evaluate the comparative effects of sertraline and vortioxetine against stress-induced brain injury in rats. Methods The rats were assigned to a nonstress group (NSG), stress-treated control (StC), sertraline + stress (SSt), and vortioxetine + stress (VSt) groups. Sertraline and vortioxetine (10 mg/kg) were given orally by gavage to the SSt and VSt groups. One hour later, all animals (except NSG) underwent forced immobilization to establish a stress model (2 hours). The drugs were given once a day for 30 days. The animals were killed with ketamine 150 mg/kg, and tissues were removed from the cerebral cortex. One-way analysis of variance and Fisher post hoc least significant difference were conducted for the analysis. Results The malondialdehyde (nmol/mL) level was 2.58 ± 0.48 in the NSG, 8.09 ± 0.57 in the StC, 3.84 ± 0.53 in the SSt, and 2.84 ± 0.20 in the VSt group (P < 0.0002). The total glutathione (mmol/g) was 7.15 ± 0.59 in the NSG, 2.41 ± 0.43 in the StC, 4.58 ± 0.26 in the SSt, and 5.98 ± 0.13 in the VSt (P < 0.0002). The total oxidant status (mmol H2O2Eq/L) level was 3.56 ± 0.20 in the NSG, 9.99 ± 0.74 in the StC, 4.97 ± 0.39 in the SSt, and 3.81 ± 0.31 in the VSt (P < 0.0002). The total antioxidant status (mmolTroloxEq/L) level was 8.65 ± 0.37 in the NSG, 3.04 ± 0.22 in the StC, 6.29 ± 0.34 in the SSt, and 7.61 ± 0.40 in the VSt (P < 0.0002). Sertraline reduced pericellular edema in astrocytes and oligodendrocytes and decreased perivascular edema, dilatation, and congestion of blood vessels, whereas these were not seen with vortioxetine. Conclusions Compared with sertraline, vortioxetine is a neuroprotective antidepressant with higher antioxidant activity and can more effectively prevent stress-induced brain tissue injury.

Morphofunctional changes in the internal organs of laying hens affected by chronic thiamethoxam intoxication

Insecticides play an important role in agriculture, general sanitary and veterinary practices, providing protection of the plants and yield from harmful insects and preventing the spread of arthropods which cause diseases in people and animals. Therefore, the objective of our study was to analyze the morphofunctional changes in the internal organs of laying hens affected by chronic intoxication with Actara 25 WG (thiamethoxam). Identification of the toxic action of theamethoxam was carried out in 150 day-old laying hens. The chronic intoxication with the insecticide was modeled by feeding mixed feed treated with the preparation in the doses that were calculated in mg of the active compound per 1 kg of body mass. The birds of the one group were the control and received mixed feed with no supplements. The hens of the first experimental group were given mixed feed that contained the insecticide in the dose of 360 mg/kg of body mass, and hens of the second experimental group consumed mixed feed containing the preparation in the dose of 180 mg/kg per body mass. We determined that laying hens of Experimental Group 1 had significant 1.24-fold decrease in the ventriculus and significant 1.39-fold increase in the spleen. Laying hens of Experimental Group 2 were observed to have increase in the absolute mass of the heart, measuring 1.36-fold compared with the control and 1.34-fold compared with Experimental Group 1. At the same time, the absolute masses of the spleen, liver, and ventriculus in Experimental Group 2 were 1.20, 1.46, and 1.19 times lower than in Experimental Group 1. Compared with the control, the absolute mass of the liver and ventriculus, was 1.54 and 1.48 times lower, respectively. Intake of feed with thiamethoxam by laying hens of the experimental groups led to decrease in the coefficient of relative mass of the liver and ventriculus. Those results significantly correlated with the absolute mass values of those organs, indicating the toxic impact of the insecticide on laying hens, with the digestive organs being the first to react. In Experimental Group 1 chickens, we observed dystrophic-necrotic changes in the liver, round-cell infiltration of the portal tracts; dystrophic-necrotic changes in epitheliocytes of the nephrons of the kidneys’; granular dystrophy of cardiomycetes, plethora of the capillaries, and stasis and edema of the stroma in the myocardium; pericellular edemas in the brain; mucous dystrophy, desquamation of the epithelium of the mucous membrane, decrease in lymphocytes in the lymphoid structures, and atrophy of the epithelium of the glandular structure in the stomach; hyperemia and necrosis of the villus tips, and round-cell infiltration of the crypt region in the thin intestine; and reproduction of cellular elements of the connective tissue between the crypts in the thin intestine. The insecticide in the dose of 180 mg/kg of body mass caused dystrophic-necrobiotic changes in the liver and kidneys; hyperemia and edema in the myocardium; pericellular edema, swelling, and vacuolar dystrophy of neurons in the brain; necrobiotic changes in the mucous membrane epithelioctes in the proventriculus; and deformation of the villi and edema of the mucous membrane in the small intestine.

Qualitative and quantitative characteristics of structures of cerebral cortex structure in young people under conditions of chronic alcohol intoxication

To study morphological changes of cerebral cortex in young people under the conditions of chronic alcohol intoxication (CAI). Morphometric examination of cerebral cortex fragments obtained from 28 persons who died with a CAI diagnosis (average age was 38 years), and 25 subjects who died from other causes, which are not associated with alcohol consumption (average age was 39 years), was carried out. It was shown that neurons of pathological shapes, including hypo- and hyperchromic, pyknotic and «shadow-like», were dominant in group of CAI. There was an increase in the glial index and a greater intensity of perivascular and pericellular edema compared to the control group. Morphological changes of cerebral cortex under the conditions of CAI are non-specific and largely similar to neurodegenerative alterations in other pathological conditions, senile dementia. Clearer histological criteria for alcoholic encephalopathy are needed, including with the use of immunohistochemical methods.

Evaluation of syringin's neuroprotective effect in a model of neonatal hypoxic-ischemic brain injury.

A significant cause of mortality and morbidity in the neonatal era is hypoxic-ischemic encephalopathy (HIE). This study examined the histopathological analysis and neuroprotective impact of syringin (SYR) in an experimental HIE rat model. On the 7th postnatal day, 24 Wistar albino rats were evaluated in 3 groups using the HIE model under gas anesthesia. In the experiment, Group A received 10 mg/kg SYR plus dimethyl sulfoxide (DMSO), Group B received DMSO only, and Group C served as a sham group. Immunohistochemical techniques were used to assess apoptotic cell measurement and proinflammatory cytokines (TNF-α and IL-1β primary antibodies). Rats suffering from hypoxic-ischemic brain damage had their apoptosis assessed. The SYR and sham groups had statistically fewer cells undergoing apoptosis (p < 0.001). There was no difference between the groups in terms of IL-1β and TNF-α during immunohistochemical staining. Neuronal degeneration was significantly lower in the histological evaluation of the hippocampus in the SYR group (p = 0.01). A statistically significant difference (p = 0.01) was observed between the SYR and the control groups regarding pericellular and perivascular edema. SYR reduced apoptosis, perivascular and pericellular edema, and neuronal degeneration in rat cerebral tissue. These results raise the possibility that SYR may have a neuroprotective effect on the harm brought on by HIE. This is the first investigation of SYR's function within the HIE paradigm.

Brain Cortex Morphology in Rats After Cold Exposures

Morphological changes of the brain cortex sensorimotor area in 6-month-old rats were studied after short-term intermittent and long-term continuous cold exposures (STICE and LTCCE, respectively). Under these conditions, perivascular and pericellular edema, small solitary foci of necrosis with gliosis phenomena, "porous" neuropil (signs under STICE at –12°С and formation during LTCCE), dystrophically changed neurons, neurons with nuclei at different stages of necrobiosis were noted in the brain tissue against the background of native cyto- and myeloarchitectonics, Some of the microvessels had signs of inflammation and thrombi. A moderate constriction (after STICE at –12°С) and a dilatation (after STICE at 10°С) of microvessels were observed. According to the fractal analysis, a decrease in the fractal dimension of the brain cortex sections was found under both STICE at –12°С and LTCCE.

MORPHOLOGICAL CHANGES OF RATS’ CEREBRAL CORTEX UNDER CONDITIONS OF DMH-INDUCED EXPERIMENTAL CARCINOGENESIS

Abstract. The progression of the endogenous intoxication syndrome accompanies the development of any neoplasm. The infl uence of toxic products leads to signifi cant disruptions in homeostasis, which seriously aff ects the central nervous system, specifi cally the cortex of the large hemispheres. Therefore, the purpose of our study was to establish changes in the morphological reorganization of the cortex of the large hemispheres of rats with DMG-induced adenocarcinoma in situ. The study used 85 mature white male rats. All animals were divided into 2 groups: I – 35 intact animals and II – 50 animals with DMG-induced colon adenocarcinoma.Histological slides of the brain were prepared by the generally accepted methodology. The drugs were studied using a MICROmed SEO SCAN light microscope and photo- documented using a Vision CCD Camera. The histological organization of the cerebral cortex of intact animals had typical histoarchitectonics. In the fi rst three stages of the experiment, moderate changes in the morphological organization of the cortex were detected compared to the control group. The fourth stage of DMG-induced carcinogenesis modeling was characterized by the manifestation of morphological changes, a decrease in the number of normochromic, an increase in hypo- and hyperchromic neurocytes, and the appearance of cell alteration signs. Typical for this period also was the progression of hemodynamic disorders: venous hyperemia, stasis, aggregation of erythrocytes («sludge»), and an increase in perivascular and pericellular edema. At the 5th and 6th stages of the experiment, a violation of the cytoarchitectonics of the cortex was revealed. Destructive changes in neurocytes increased. Betz cells were in a state of tigrolysis, sometimes in total one. A decrease in the Nissl substance in neurons confi rmed their impaired functional capacity. Increased permeability of capillary walls led to severe pericellular edema of neurocytes. Intracellular edema was also detected in most neurocytes. The 7th stage of the induced carcinogenesis was characterized by the presence of severe destructive changes in neurons: an increase in the number of hypo-, hyperchromic, sharply hypo-, and sharply hyperchromic neurocytes, a fragmentation of neurocyte neuroplasm, most of Betz cells in a state of total tigrolysis, a decrease in the content of Nissl substance in them, up to its complete absence. Blood capillaries had a deformed wall and signifi cantly enlarged perivascular spaces. Consequently, the study established the development and dynamics of alterative changes in the neurocytes of the cerebral cortex caused by DMG-induced carcinogenesis. These disorders were characterized by alteration of neurocytes and progressive microcirculation disorders. All identifi ed morphological changes in the brains of aff ected animals prove their dependence on the duration of carcinogen exposure.&#x0D;

Post-Morther Changes in Rat Paretial Cortic and Hippocampus Neurons. Morphological Characteristics

Target. Analysis of changes in the morphological characteristics of neurons in such phylogenetically different parts of the rat cerebral cortex in different periods after total cerebral ischemia. Methodology. Experiments were performed on 42 male outbred white rats with an initial weight of 240±20 g. Total cerebral ischemia in outbred white rats was modeled by decapitation. The material was taken at the 1st, 5th, 15th, 30th, and 60th minutes, as well as 5 and 24 hours after decapitation. Results. With total cerebral ischemia, a significant decrease in the size of neurons and deformation of the perikarya were observed. Normochromic neurons completely disappeared at the 60th minute. The number of hyperchromic neurons increased and then progressively decreased. Shriveled neurons accounted for the majority of cells in the studied areas of the cortex at 30-60 minutes, and then, after 5 and 24 hours, cells with pericellular edema predominated in the neuron population. Conclusion. The obtained data on histological changes in neurons of phylogenetically different parts of the cerebral cortex in the dynamics of total cerebral ischemia provide the basis for further detailed study of post-mortem changes in the brain, determining the time of death, creating a fundamental basis for studying the properties of neurons, including their transition from one functional state to other.

CHANGES IN THE SENSORIMOTOR CORTEX OF THE RAT BRAIN UNDER THE MODELING OF HEMORRHAGIC STROKE.

The aim: To assess the structural and metabolic changes in the sensorimotor cortex of the rat brain under conditions of hemorrhagic stroke. Materials and methods: The experiment was carried out on rats of the control and experimental groups with a model of hemorrhagic stroke. We used histological, electron microscopic, biochemical methods and biological markers. Results: In the sensorimotor cortex of the ipsilateral cerebral hemisphere of rats under conditions of hemorrhagic stroke, cerebral edema and progression of neurodegenerative changes were observed; an increase in the size of mitochondria, which is caused by edema of their matrix; activation of lipid peroxidation processes and a decrease in the activity of enzymes of the antioxidant system, a decrease in the level of apoptosis markers and inhibition of ERK1/2 expression. The study of DNA fragmentation in the cerebral cortex revealed a significant number of manifestations of necrosis and an insignificant number of cells in a state of apoptosis. Conclusions: after modelling a hemorrhagic stroke in the right hemisphere of the brain, perivascular and pericellular edema of the energy apparatus, cell death by necrosis and apoptosis, and activation of lipid peroxidation processes were established as well as a decrease in the activity of enzymes of the antioxidant system.

DYNAMICS OF MORPHOLOGICAL CHANGES IN CELLS OF THE CEREBELLUM IN ACUTE POISONING WITH CLOZAPINE IN COMBINATION WITH ALCOHOL

According to most researchers, the central mechanism of clozapine poisoning in combination with alcohol is their cholinolytic effect. A life-threatening condition with clozapine occurs as a result of an unintentional overdose of the prescribed drug, suicidal behaviour, or criminal behaviour. Despite the urgency of the problem of clozapine poisoning in combination with alcohol, the pathogenesis of these conditions and the resulting morphological changes in the brain have not been sufficiently investigated. In this connection, the purpose of our experimental research is the study of the dynamics of changes in Purkinje cells of the cerebellum in the early period of acute poisoning with clozapine in combination with alcohol. In sections of the cerebellum of the control group, reversible changes in Purkinje cells (15–20%) predominated in the form of primary irritation and acute swelling. Irreversible damage to Purkinje cells (2-5%). 3 hours after poisoning with clozapine in combination with ethanol, Purkinje cells showed irreversible damage to cerebellar cells with signs of severe changes, neuronophagia, and pericellular edema, with the following ratio: reversible 25-30% and irreversible 60-70%. 24 hours after the combined poisoning with clozapine in combination with alcohol, in percentage terms, the ratio of the changes was the following: reversible 25-30% and irreversible 60-70%. The study revealed the dynamics of reversible and irreversible changes in Purkinje cells with a predominance of irreversible damage was established, especially after 24 hours from the start of the experiment.

Syndrome of hyperosmolar hypohydration in the experiment: features of morphological disorders in brain tissues of rats with homeostasis disorders of different degrees of severity

Annotation. In neurosurgical patients, damage to the hypothalamic-pituitary region in 30% of cases can be complicated by the development of central diabetes insipidus, manifested by gross disturbances of the water-salt balance: the development of hypertonic hypohydration, which leads to functional and structural damage to organs and tissues. The purpose of the study was to simulate in an experiment the syndrome of hyperosmolar hypohydration, to investigate the peculiarities of morphological changes in brain tissues of animals depending on the level of osmolarity of blood plasma. To simulate hyperosmolar hypohydration, laboratory rats were injected intraperitoneally with furosemide solution (5.0 mg per kg-1), and under anesthesia intravenously – 2.0 ml of hyperosmolar sodium chloride solution of various concentrations (from 1.8% to 9%). The degree of hypohydration of the body, degree of hyperosmolarity, duration of coma, and lethality were studied. Pieces of the brain tissue were taken for histological examination, and their processing was carried out according to generally accepted methods. Histological slides were studied using a SEO SСAN light microscope. In hyperosmolar coma, under the conditions of administration of 7.2% sodium chloride solution to rats, blood-filled vessels with moderate perivascular edema were found in the brain tissues. Heterogeneous changes were characteristic of neurocytes, among them there were normochromic, isolated hypochromic and a significant number of hyperchromic neurocytes, and pericellular edema was detected. In brain tissues in hyperosmolar coma caused by the administration of 8.1% sodium chloride solution, an increase in amount of blood in vessels with pronounced erythrostasis was found, and small isolated hemorrhages were identified. Perivascular edema was significant in most of the vessels. Karyopyknosis and hyperchromatosis were characteristic of neurocytes, significant pericellular edema was also detected. In the tissues of the brain, in hyperosmolar coma, caused by the introduction of 9.0% sodium chloride solution, an increased amount of blood-filled vessels with pronounced erythrostasis was observed. Vessels walls were with pevascular edema, plasmarrhagia was also marked. In most fields of vision, hyper- and sharply hyperchromic neurocytes were identified, which were characterized by compaction, pyknosis, and pericellular edema. In brain tissue in hyperosmolar coma caused by intravenous administration of 7.2%, 8.1% and 9.0% solutions of sodium chloride, the appearance and progression of the following histological changes were established: blood-filled vessels, erythrostasis, small diapedesis hemorrhages, significant pevascular edema due to plasmarrhagia. Heterogeneous changes in neurocytes, with the appearance and predominance of hyper- and sharply hyperchromic cells, and significant pericellular swellings were established.

Changes in respiration of the mitochondrial fraction of brain homogenates in rats with stepwise incomplete cerebral ischemia

Objective: to conduct a comparative analysis of mitochondrial respiration in brain homogenates of rats with stepwise incomplete cerebral ischemia (SICI) with varying duration between ligations of both common carotid arteries (CCA). Material and methods. The experiments were performed on 24 male mongrel white rats weighing 260±20 g. All rats were distributed among three subgroups. Cerebral ischemia was simulated under intravenous thiopental anesthesia (40-50 mg/kg). The control group (n=6) comprised sham-operated rats of similar gender and weight. To study mitochondrial respiration, the brain was extracted in the cold environment (0-4 °C), dried with filter paper, weighed and homogenized sensu the modified technique in an isolation medium containing 0.32 M sucrose, 10 mM Tris-HCl, 1 mM EDTA, pH of 7.4 (in a ratio of 1:10), using Potter – Elvehjem homogenizer with Teflon pestle. Results. SICI with an interval of 1 and 3 days between ligation of both CCA led to neuronal damage in the parietal cortex and hippocampus of rats, which manifested itself in a reduction of the neuron size, deformation of the perikaryons, an increase in the number of shrunken neurons and shadow cells. The most pronounced changes were observed in the subgroup with one-day interval between ligations. These changes were similar to the changes in incomplete cerebral ischemia (ICI) (p=0.07), except for the absence of cells with pericellular edema in the hippocampus and a smaller number of those in the parietal cortex. ICI with seven-day interval between ССА ligations, on the contrary, was manifested by less pronounced histological changes, especially in the hippocampus. Conclusion. Comparative analysis of mitochondrial respiration in brain homogenates revealed that the severity of brain damage in SSIC depended on the interval between blood flow arrest in both CCA. At the same time, the highest level of energy metabolism disorder was observed during CCA ligation with an interval of one day, which implied insufficient implementation of compensatory mechanisms.

Diaphragm Function Parameters in Patients with Severe COVID-19

The aim of the study was to investigate the feasibility of predicting the need for mechanical ventilation in patients with severe COVID-19 disease using ultrasound assessment of diaphragm function.Material and methods. An open prospective pilot study included 60 patients diagnosed with the novel coronavirus infection, who, at the time of admission to the intensive care unit (NEWS score &gt; 6), underwent ultrasound assessment of diaphragm excursion, thickness and the diaphragm thickening fraction. Group 1 (n=30) included patients who did not require mechanical ventilation, and group 2 (n=30) consisted of patients who were subsequently transferred to mechanical ventilation.Results. Patients in group 2 had significantly lower diaphragm function parameters (left excursion value (P&lt;0.001), right excursion value (P&lt;0.001), diaphragm thickness on inspiration (P=0.043), and thickening fraction (P&lt;0.001) than patients in group 1.Conclusion. Decreased diaphragm excursion of less than 17.1 mm on the right side is a predictor of initiation of mechanical ventilation in patients with the COVID-19 infection (sensitivity 93.3%, specificity 76.7%). Morphological examination in deceased patients of group 2 revealed pericellular and perivascular edema, venular thrombosis, endoneurial edema, and sludge in the lumen of arterioles.

Stepwise Cerebral Ischemia Causes Disturbances in Mitochondrial Respiration of Neurons in the Cerebral Cortex of Rats

Objectives: To conduct a comparative analysis of respiration of mitochondria of brain homogenates of rats with stepwise subtotal cerebral ischemia with different duration between ligations of both common carotid arteries. Methods: The experiments were performed on 24 male mongrel white rats weighing 260 ±20 g. Cerebral ischemia (CI) was simulated under intravenous thiopental anesthesia (40-50 mg/kg). The control group consisted of falsely operated rats of similar sex and weight. To study mitochondrial respiration, the brain was extracted in the cold (0-4°C), dried with filter paper, weighed and homogenized in an isolation medium containing 0.32 M sucrose, 10 mM Tris-HCl, 1 mM EDTA, pH 7.4 (in a ratio of 1:10), using Potter-Evelheim homogenizer with Teflon pestle according to the modified method. To prevent systematic measurement errors, brain samples from the compared control and experimental groups of animals were studied under the same conditions. Results: Stepwise SCI with an interval of 1 and 3 days between bandages of both OCA leads to damage to the neurons of the parietal cortex and hippocampus of rats, which manifests itself in a decrease in their size, deformation of the pericaryons, an increase in the number of shrunken neurons and shadow cells. The most pronounced changes were observed in the subgroup with an interval between dressings of 1 day. These changes were similar to the changes in SCI (p&gt;0.05), except for the absence of cells with pericellular edema in the hippocampus and a smaller number of them in the parietal cortex. SCI with an interval between WASP dressings of 7 days, on the contrary, it is manifested by less pronounced histological changes, especially in the hippocampus. Conclusion: In cerebral ischemia, damage to the inner mitochondrial membrane occurs due to activation of free radical oxidation processes. Damage to the inner mitochondrial membrane, in turn, leads to an increase in its permeability and a decrease in the level of the proton gradient due to the transition of protons along the concentration gradient through the resulting nonspecific pores into the mitochondrial matrix. As a result, the efficiency of ATP synthesis decreases, and more substrates and oxygen are required to maintain the intermembrane potential under these conditions.

The effect of (Mg, Co) bis (citrate) germanates on morphological changes in brain tissue

Introduction. The problem of safety of pharmacotherapy is becoming more and more urgent all over the world. This is primarily due to the increase in the number of medicines and their widespread use. The use of pharmacotherapeutic agents is usually accompanied by the occurrence of adverse reactions, which differ in their manifestations and degree of severity. Safe use of medicines is one of the priority tasks of modern health care. Therefore, when studying new biologically active substances – future medicines, special attention is paid to information about their toxicity. The search for new effective and safe medicines is a rather complex and long process. One of the well-known ways of searching is based on the detection of biologically active substances (BAS) involved in life processes, pathophysiological and pathochemical processes that underlie the pathogenesis of various diseases. Guided by these principles under the leadership of Professor Seyfullina I.Y. at the Department of Inorganic Chemistry and Chemical Education of Odesa National University named after I.I. Mechnikov, a number of biologically active substances were synthesized – coordination compounds based on germanium, vitamins, microelements, and organic acids acted as bioligands. Purposefully synthesized: magnesium bis(citrato)germanate – hermacite, cobalt bis(citrato)germanate – hercocite. The acute toxicity of BAR was studied: magnesium bis (citrato) germanate LD50= (3049.55±42.54) mg/kg of rat weight, cobalt bis (citrato) germanate LD50= (185.00±4.23) mg/kg. The aim of the work was to study the morphological changes in the brain tissue of rats after administration of (Mg, Co) bis (citrate) germanates in subacute and subchronic experiments. Research methodology and methods. An experimental study was conducted on sexually mature male Wistar rats weighing 180-250 g, which were injected intraperitoneally with (Mg, Co) bis (citrate) germanates in doses of 1/40, 1/110 and 1 /135 LD50. At the same time, it was previously proven that the main pharmacological properties of the compound were manifested by doses of 1/110 and 1/135 LD50. After decapitation, macro- and microscopic examination of the brain tissue was carried out. When conducting the experiment, the general principles of the European Convention for the Protection of Vertebrate Animals, Directive 2010/63/EU of the European Parliament and the Council of the European Union dated September 21, 2010 on the protection of animals used for scientific purposes were observed. Research results and their discussion. The introduction of coordination compounds of metals for 28 days at a dose of 1/40 LD50 caused the appearance of perivascular and pericellular edema in the tissue of the brain, which was more pronounced for the cobalt-containing compound. Administration of hermacyt in doses of 1/40 LD50 for 3 months led to the appearance of areas of necrotized brain tissue, and administration of hercocyte led to the appearance of areas of destruction of brain tissue with the formation of small cavities. Administration of BAR in doses of 1/110 LD50 for 28 days and 3 months was accompanied by minor morphological changes (moderately expressed perivascular and pericellular edema). When BAR was used in doses of 1/135 LD50, the tissue of the brain of rats had minor changes (fullness of individual vessels of the microcirculatory channel, around which there is moderate edema). Conclusions. Thus, new multimetallic coordination compounds (Mg, Co) bis(citrate) germanate in effective doses in subacute and subchronic experiments did not show toxic effects on brain tissues and are promising for further study and establishment of pharmacological properties.

Вибухо-індукована нейротравма (патофізіологічні та патоморфологічні особливості)

The article presents the results of pathophysiological and pathomorphological features which were studied in experimental blust-induced neurotrauma in rats. The relevance of this study is associated with the frequent blust neurotrauma resulting from the use of explosives in military conflicts. At the same time, neurotrauma is more common, which is clinically manifested by cognitive impairment, even with mild and moderate severity. This, in turn, leads to complications and disability for young people. The purpose of the work was to study the consequences of the air-shock wave influence on the functional and morphological states of the central nervous system. Materials and methods. The studies were carried out on 36 white male Wistar rats 5-7 months old, weighing 180-220 g. The rats were divided into two groups: I – experimental group (n=18), the animals of which were anesthetized with halothane, fixed and explosion-induced neurotraum was simulated by generating a baroacoustic wave with an excess pressure of 26.4 ± 3.6 kPa. II group was a control group (n=18). Functional changes were investigated in the Barnes maze. For pathomorphological examination, brain sections were stained with hematoxylin and eosin. The animals were kept in standard conditions and in the standard diet of the vivarium, all studies were conducted in accordance with modern international requirements and norms of humane treatment of animals (Council of Europe Convention dated 18.03.1986 (Strasbourg); Helsinki Declaration 1975, revised and supplemented in 2000, Law of Ukraine dated 21.02.2006 No. 3447-IV), which is evidenced by an extract from the protocols of the meeting of the commission on biomedical ethics. Results and discussion. Analysis of the results of memory studies in the Barnes maze showed a significant (Р &lt;0.05) increase in the latent time of entering the shelter in rats of the experimental group in the acute and early post-traumatic period, which indicates memory impairment. General characteristics of the rats behavior in the experimental group showed an increase in anxiety and disorientation. The increase in research on "fake shelters" and the chaotic movement around the facility was evidenced. Analysis of frontal histological sections of the rat brain in the dynamics of the explosion-induced neurotrauma development showed the presence of characteristic signs in the form of diffuse microhemorrhages in the hippocampus zone in the acute period of injury, diffuse areas of perivascular and pericellular edema in the early post-traumatic period and paretic dilated capillaries in the structure of the cerebral region on 2nd-3rd week of the post-traumatic period. Conclusion. Thus, quantitative (increased latent time) and qualitative (increased anxiety) signs of impaired orientational-spatial memory and the development of specific pathomorphological signs of explosive brain damage in rats of the experimental group were established

Морфологічні зміни головного мозку при діабетичній енцефалопатії

Метою наведеної роботи було вивчення морфологічних характеристик змін головного мозку у хворих із діабетичною енцефалопатією (ДЕ) на підставі дослідження аутопсійного матеріалу. Матеріали та методи. В роботі наведено результати 14 секційних спостережень. Середній вік хворих становив 51,0 ± 3,4 року. Шматочки мозку фіксували в розчині IHC Zink Fixative, виготовляли серійні парафінові зрізи товщиною 10 ± 1 мкм. Препарати фарбували гематоксиліном і еозином, конго рот, тіоніном за методом Ніссля, ставили ШИК-реакцію, імпрегнували нітратом срібла за методом Більшовського і хлоридом золота за Кахалем, проводили морфометричне дослідження за Г.Г. Автанділовим. Препарати досліджували на мікроскопі Olympus AX70 з цифровою камерою Olympus DP50. Мікрофотографування препаратів здійснювалося з використанням програми AnalysisPro 3.2. Результати. Основними цито-ангіоархітектонічними проявами ДЕ є дифузна альтерація базальних мембран і ендотелію судин мікроциркуляторного русла, меншою мірою — артеріол, внутрішньомозкових артерій і вен. Висока щільність (питомий обсяг) капілярної мережі при ДЕ морфологічно відображає картину капілярного паралітичного застою. Капілярний застій супроводжується стазом крові, збільшенням навколосудинного капілярного простору (простір Вірхова — Робіна), ширина якого є морфологічним еквівалентом лімфатичної дисциркуляції. Ранні морфологічні ушкодження стінок капілярів — потовщення і розщеплення основної мембрани з накопиченням ШИК-позитивних речовин, вогнищева проліферація ендотеліоцитів. До пізніх пошкоджень відносяться капілярний фіброз і гіаліноз, проліферація перицитів, що супроводжується різким порушенням транскапілярного транспорту. Порушення стріарної і радіарної цитоархітектоніки в I–IV шарах головного мозку, випадіння нейронів (нейрональні спустошення) проявляються вогнищевим випадінням гангліозних і пірамідальних клітин. Висновки. Ранніми зворотними морфологічними змінами нейронів є набухання нейронів (гідропічна дистрофія нервових клітин), вогнищевий гіперхроматоз. Незворотними структурними ушкодженнями нейронів є лізис ядра і ядерця з гомогенізацією цитоплазми, формування клітин-тіней, вакуолізація цитоплазми, перицелюлярний набряк, лізис відрост­ків у поєднанні з нейрофагією. Є характерним поєднання гострих альтернативних ушкоджень нейронів із хронічними (ішемічного характеру) — пікноз, зморщування ядер з вираженою атрофією цитоплазми.

Brain Morphological Changes in COVID-19

The aim of the study was to identify the pathomorphology of brain damage in patients who died of COVID-19.Material and methods. Autopsy reports and autopsy brain material of 17 deceased patients with pre-mortem confirmed COVID-19 infection were analyzed. Fatal cases in which COVID19 was the major cause of death were included in the study. Five people were diagnosed with cerebral infarction. Organ samples were taken for histological examination during autopsy. Sections were stained with hematoxylin and eosin and by Nissl to assess brain histopathology. To study the vascular basal membranes the PAS reaction was used, to detect fibrin in vessels phosphotungstic acid-hematoxylin (PTAH) staining was used, to determine DNA in nuclei sections were stained according to Feulgen, to detect RNA in neuronal nuclei and cytoplasm sections were stained with methyl green-pyronin. Immunohistochemical study of a neuronal marker, nuclear protein NeuN, was performed to assess neuronal damage.Results. The signs of neuronal damage found in patients who died of COVID-19 included nonspecific changes of nerve cells (acute swelling, retrograde degeneration, karyolysis and cytolysis, ‘ghost' cells, neuronophagia and satellitosis) and signs of circulatory disorders (perivascular and pericellular edema, diapedesis, congested and engorged microvasculature).Conclusion. Brain histopathological data indicate damage to the central nervous system in COVID-19 patients. Ischemic stroke in patients with COVID-19 is mostly caused by a combination of hypoxia resulting from respiratory failure and individual risk factors, including cerebrovascular atherosclerosis and hypertension.

Expression of protective proteins and morphological changes in the rat brain after prolonged exposure to dust

Introduction. The fundamental mechanisms of the body's pathological reaction to coal and dust exposure are hypoxia, excessive activation of free radical processes, structural and metabolic disorders in various organs. Organ-specific molecular defense mechanisms begin to function in the form of changes in the level of proteins with antihypoxic (HIF-3a), chaperone (HSP72), and antioxidant functions (HOx-1 - heme-oxygenase, Prx-1 - peroxiredoxin) under damaging effects. Its high level contributes to the restoration of cells' functional state or indicates significant damage in tissues. Hypoxia and free radical processes are known to lead to severe brain damage and behavioral disorders. To date, little is known about the expression of protective proteins and morphological changes in the brain under prolonged exposure to coal-rock dust on the body. The study aimed to learn the level of intracellular protective proteins HIF-3a, HSP72, HOx-1, Prx-1, and morphological changes in the brain in the dynamics of long-term dust exposure. Materials and methods. Sixty white male Wistar rats weighing 200-250 g of the same age took part in the experiment. Dust exposure was modeled by way of dynamic inhalation priming of rats with coal-rock dust (coal of a gas-fat brand) in an intermittent mode for 12 weeks. We perform morphological studies of the brain after 1, 3, 6, 9, and 12 weeks of dust exposure. The cytosolic fraction of brain tissue researchers determined the expression level of HIF-3a, HSP72, HOx-1, and Prx-1 by Western blot analysis. We selected the activity of free radical processes in the brain tissue. Results. Long-term exposure to coal-rock dust on the body at the morphological level in the brain revealed changes that indicate the development of hypoxia and activation of free radical processes: microvascular disorders, pericellular edema, severe dystrophic damage to neurons, focal loss of neurons, activation of glial cells. Activation of the protective proteins HIF-3a, HSP72, HOx-1, and Prx-1 in the early stages (1-3 weeks) of coal-dust exposure provided compensation for free radical processes in brain neurons. An increase in the duration of dust exposure of more than six weeks influences a low level of HSP72, but high HIF-3a and Prx-1, indicating an increase in hypoxic and free radical damage brain. Conclusions. The results obtained to expand the understanding of the morphological and molecular mechanisms that occur in the brain tissue during prolonged dust exposure to the body are essential for developing methods for organ-specific pharmacological correction.

Epiplexus phagocytes of nervous tissue in experimental brain contusion

Neuroinflammation is known to participate in pathogenesis of intracranial brain injury (TBI), e.g., brain contusion or concussion. In view of high overall prevalence of these conditions, there is a need for nosological verification of the mild- and moderate-severity neuroinflammation. Our research in immune regulation of blood flow in TBI, including a role of Kolmer cells in pathogenesis of neuroinflammation, is now at the stage of collecting research data and requires adequate experimental study. Purpose of our study was as follows: to assess the state of Kolmer cells in vascular plexus of brain ventricles in experimental model of mild traumatic brain contusion (mTBC). mTBC was reproduced in male Wistar rats using a model of a falling load weighing 200 g. Immunohistochemical study was performed in order to assess CD45 receptor expression on the brain cells. During acute period after mTBC, we observed constriction of blood vessels and pericellular edema of the brain tissues. Expression of CD45 cytodifferentiation receptors markers characteristic of the hematopoietic cell pools was found in parenchymal areas of neocortex and on the surface of choroid plexuses in brain ventricles. These data suggest participation of epiplexus and parenchymal macrophages in the pronounced pericellular edema of the brain. On the 8th day of observation, the spasm of the blood vessels persists, along with significantly weaker pericellular edema. In all the brain sections, leukocyte infiltration of tissues was not seen, and there was no expression of CD45 receptors, whereas increased number and size of nucleoli was found in the neurons. The results of our study confirm the role of cerebral vasospasm as a severe complication of neuroinflammation developing after mTBI. Acute inflammation is characterized by a series of vascular changes, manifesting by development of vasospasm, arterial, venous hyperemia and stasis. Venous hyperemia is characterized by further vasodilation, tissue plethora, the phenomenon of the marginal leukocyte stasis and their emigration, along with increased exudation processes. Innervation from subcortical neurons or local cortical interneurons to parenchymal arterioles and cortical microvessels provides minimal contact and predominantly targets the surrounding astrocytes and other cells. During acute period of mTBC, the inflammatory process is confirmed by the presence in parenchyma and on the surface of ependymal Kolmer cells and by expression of CD45 receptors. This finding points to inflammatory reasons for altered tone of pial blood vessels, capillaries of neocortex and ependymal areas, and changed depth of subarachnoid space. Response of astrocytes to the brain trauma could be another factor of neuroinflammation.

Microscopic changes in the neurocytes of the cerebellar cortex in dynamics under conditions of experimental thermal injuryc

Summary. Thermal injury as a stress factor of exogenous origin, in which the development of multiple organ failure and dysfunction of organs and systems of the body occur. The nervous system is one of the first to perceive and respond to pain impulses. It is important to reorganize all the structural components of the microcirculatory tract and neurons as a result of endogenous intoxication, which develops during thermal trauma. The target of lesions is the cerebellum, as a multifunctional organ of the central nervous system. The aim of the study – to establish the microscopic reorganization of neurocytes of the cerebellar cortex in the dynamics under conditions of experimental thermal trauma to the skin. Materials and Methods. The experimental study was performed on 24 adult white male rats weighing 180–200 g. Simulation of third-degree burns was performed with copper plates heated in boiled water to a temperature of 97–100º on the epilated surface of the skin of animal bodies under thiopental sodium. The size of the affected areas was 18–20 % of the body of rats. Collection of material for microscopic examination was performed in accordance with generally accepted methods. Histological sections obtained on a sled microtome 5–6 μm thick were stained with hematoxylin and eosin, toluidine blue by the method of Nissl. Semi-thin sections made on an ultramicrotome LKB-3 were stained with methylene blue. The micropreparations were studied using a MICROmed SEO SCAN light microscope and photo-documented using a Vision CCD Camera with a histological image output system. Results. Microscopic studies have shown an interdependence between the duration of the experiment and abnormalities in the structural components of neurons in all layers of the cerebellar cortex. In the early stages of the experiment there are reactive changes, which are adaptive-compensatory in nature with initial destructive damage. On day 14, and especially after 21 days, polymorphism is observed, significant cell degeneration, manifested by pycnosis of the nuclei, the development of intra- and pericellular edema in neurons of the granular, ganglionic and granular layers of the cerebellar cortex