Objective. The aim of this study was to assess the vascular endothelium morphofunctional state of the brain microcirculatory bed in rats with nitrite-induced Alzheimer's type dementia on the background of stem cells administration. Methods. 14 days after the experiment's end, the endothelin-1, VEGF-A, eNOS, von Willebrand factor were determined in blood serum by the enzyme immunoassay and photometric methods in rats with a model of nitrite-induced dementia (14 and 28 days of sodium nitrite intraperitoneal introduction) with and without mesenchymal stem cells (MSCs) administration. The brain slices were stained according to the Einarson's method and immunohistochemically by staging the reaction with antibodies to VEGF. Results. With an increase in the sodium nitrite administration period, the degree of damage of brain capillaries and neurons increased, dystrophy of "surviving" neurons developed and ability to produce VEGF decreased. After 14 days of "regeneration period" in groups without MSCs administration, further stimulation of VEGF production by endotheliocytes, cortex and hippocampus neurons of varying degrees was observed. In groups where stem cells were introduced, the number of capillaries increased, with endothelial hyperplasia in some cases. Conclusion. In animals with nitrite-induced dementia, dose-dependent damage to the endothelium of the capillary bed is noted. From the first day damage the vascular regeneration can be proved by VEGF expression. The stem cells administration more effectively stimulates capillary regeneration, as evidenced by a noticeable increase of the number of brain capillaries.
Background. The last researches offer to conduct the study of Alzheimer disease (AD) mechanisms using diverse experimental models. However, it was not investigated the behavioral and cognitive impairment in rats at the different stages of vascular model of dementia of Alzheimer’s type developed by us.
Subjects and methods. The experiment was performed on 32 male WAG rats weighing 180-250 g which were divided into 4 groups. Rats from group 1 and 3 were injected by aqueous solution of sodium nitrite at a dose of 50 mg/kg of body mass intraperitoneally during 14 and 28 days respectively. Groups 2 and 4 were received 500,000 mesenchymal stem cells in suspension intravenously against the background of experimental nitrite-induced AD. To estimate the behavioral reactions and cognitive functions the Open Field Test (OFT) and Passive Avoidance test (PAT) were used.
Results. In all experimental groups in most cases it was found the significant decrease in vertical and horizontal activity (p <0,05) and an increase in the number of defecation in the OFT. Rats from group 3 had the drop in locomotor, research and orientation activity. In the OFT and PAT in groups 2,4 it was observed an improvement in research activity and significant cognitive functions recovery (p=0,012) after stem cell correction.
Conclusions. It was found the progression of the protective inhibition and cognitive impairment during experiment. The stem cells introduction had positive effects on brain function recovery.
The cerebral hemispheres neuropil of rats with experimental nitrite-induced Alzheimer’s type dementia was studied after mesenchymal stem cells (MSC) introduction. Rats were injected with an aqueous solution of sodium nitrite (50 mg/ kg) for 14 (group 1) and 28 days (group 3), and half of them additionally got intravenously MSC (500000 cells per rat) (groups 2 and 4). The control group received saline in the same way. The acetylcholine level, TBA-active substances contents, catalase and superoxide dismutase activities in brain homogenates, and the content of 2,3-diphofoglycerate (2,3- DFG) in erythrocytes were measured spectrophotometrically. Brain slices were stained with Congo red and according to the Einarson method. They were then examined on an Axiostar plus binocular microscope (“Zeiss”, Germany). The optical density of the cerebral hemispheres neuropil had been measured. In all experimental groups, an increase in the content of 2,3-DFG in erythrocytes and an imbalance in the pro- and antioxidant system, oxidative stress development in brain were observed. The neuropil structure of the cerebral hemispheres was changed: we observed focal zones of neurofilaments degeneration and atrophy and amyloid accumulation, especially in group 3. The optical density of neuropil was reduced; this was accompanied by a decrease in the content of acetylcholine. MSC injections resulted in a significant increase in the content of acetylcholine, decrease in the brain oxygen demand and the content of TBA-active substances. Consequently, prolonged sodium nitrite administration leads to the cerebral hemispheres neuropil structure and functional injury. MSC introduction contributes to the improvement of the neuropil morphofunctional state.
The role of the imbalance of regulatory cytokines in the blood of rats under conditions of chronic immobilization stress, compared with the control, in the implementation of immune mechanisms of pancreatic damage was considered, where it was established:
На моделі хронічного стресу спричиненого довготривалою іммобілізацією щурів-самиць в період вагітності, встановлено, що у тканині підшлункової залози і сироватці крові не тільки їх самих, а й їх одно- та двохмісячного потомства відзначається зсув основних показників оксидантно-антиоксидантного гомеостазу, що, можливо є результатом реалізації нейрогуморальної відповіді організму на стрес. Ці зміни не є ідентичними у сироватці крові і тканині підшлункової залози тварин, а інформативність показників оксидантно-антиоксидантного гомеостазу сироватки крові, що використовується для кращого розуміння аналогічних змін в тк анині підшлункової залози, є відносною.
The hematoophthalmic barrier is one of the mechanisms of resistance that serves to protect the body and prevents homeostasis disorder when the body is affected by factors that can disturb this balance. One of the complications of mechanical trauma of the eye and violation of the hematoophthalmic barrier is the appearance of oxidative stress on the background of the general inflammatory process in violation of cellular structures. Objective: to study the dynamics of catalase activity in the heart and muscle tissue of rats under oxidative stress caused by mechanical action on the hematoophthalmic barrier. Materials and methods. The study was carried out on white neonatal mature healthy male rats of six months of age, weighing 200–220 g and having 150 pieces. The activity of catalase in heart and muscle tissue was studied before the beginning of the experiment, as well as on the 1st, 3rd, 5th, 7th and 14th day of the experiment using the standard Korolyuk M.A. method. The dynamics of catalase activity was evaluated by different methods of treatment of mechanical eye trauma, including the use of quercetin antioxidant. The results of the study. It was found that in addition to the standard therapy of mechanical eye injury injection of quercetin, the activity of catalase in the heart and muscular tissue after falling on the background of induced oxidative stress increases to the values of physiological norm by 14 days, which indicates the effective elimination of oxidative stress. Conclusions. The activity of catalase in rat heart and muscle tissue under oxidative stress caused by mechanical influence on hematoophthalmic barrier is most effectively stabilized under standard therapy of mechanical eye injury with addition of quercetin in the form of injections.
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