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

2022 ◽  
Vol 3 (1) ◽  
pp. 01-05
Author(s):  
Bon L.I ◽  
Maksimovich N.Ye ◽  
Dremza I.K. ◽  
Lychkovskaya Maria A

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>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.

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
George Wong ◽  

Background and purpose: Disability is common after severe stroke resulting from major cerebral artery occlusion despite adoption of prophylactic decompressive craniectomy. Experimental mesenchymal stem cell treatments are commonly administrated through systemic infusion, with limitations in dosage. In this study, the neuro-modulation effect of topical mesenchymal stem cells (MSCs) was tested in a rodent middle carotid artery occlusion (MCAO) model. Methods: Twenty-four hours after MCAO, craniotomy was made and 0.8 x 10 6 GFP-MSCs were topically applied to the ipsilateral parietal cortex (N=30). In the control group, saline were topically applied to the ipsilateral parietal cortex (N=30). Results: After topical MSC treatment, neurological assessments with Rotarod test (at days 3, 7, and 10) and Morris Water Maze test (at days 3, 7, and 14) were significantly better, as compared to the control group; the infarct volume was also smaller. MSCs were found in the penumbra of the infarct 3 days after topical application. In the PCR array analysis of the RNA extracted from penumbra cortex, topical application of MSCs changed 10 gene expressions in the penumbra at day 3 (fold change >1.25, p<0.05 after Bonferroni corrections for multiple comparisons). The seven up-regulated genes (Apoe, Ascl1, Efnb1, Mef2c,Nog,S100a6, B2m) involve neuronal migration, neuronal differentiation, neuronal cell fate determination, regulation of synaptic plasticity, axonogensis;, growth factors, and cell adhesion. Pax2, Pax3 and Th were downregulated. Pax2 and Pax3 are related to apoptosis. Both Apoe and Thl involve synaptic transmission. Conclusions: Topically applied MSCs reduced cerebral infarction volume and improved the neurological function from cerebral ischemia resulting from a major cerebral artery occlusion in a rodent experimental model.


1987 ◽  
Vol 65 (12) ◽  
pp. 1057-1063 ◽  
Author(s):  
Rafael Villalobos-Molina ◽  
J. Pablo Pardo ◽  
Alfredo Saavedra-Molina ◽  
Enrique Piña

The permeability of the inner mitochondrial membrane from rat liver to D-arginine was studied. By using safranin as a probe of the membrane potential, depolarization of energized liver mitochondria occurred in a dose-dependent fashion starting at 3.3 mmol/L of D- or DL-arginine. When ethidium bromide fluorescence was employed, a decrease in the membrane potential due to D- or DL-arginine was observed. A parallel significant change in succinate-induced respiration in rat liver mitochondria was found in response to osmotic swelling in 125 mmol/L of D-arginine salts. L-Arginine, L-glutamine, L-asparagine, L-ornithine, D-ornithine, and L-lysine did not modify the membrane potential at the concentrations tested. D-Arginine was not transformed into citrulline, but 1.0 mmol/L of the D-amino acid inhibited, by 42%, the state 3 of mitochondrial respiration using succinate as substrate. When D-arginine was used in combination with nigericin, a 40% inhibition of mitochondrial respiration in state 3 was recorded with succinate and with glutamate–malate as substrates.


2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Haixia Wen ◽  
Luxi Li ◽  
Lixuan Zhan ◽  
Yunyan Zuo ◽  
Kongping Li ◽  
...  

AbstractMitophagy alleviates neuronal damage after cerebral ischemia by selectively removing dysfunctional mitochondria. Phosphatase and tensin homolog (PTEN) induced putative kinase 1 (PINK1)/Parkin-mediated mitophagy is the most well-known type of mitophagy. However, little is known about the role of PINK1/Parkin-mediated mitophagy in ischemic tolerance induced by hypoxic postconditioning (HPC) with 8% O2 against transient global cerebral ischemia (tGCI). Hence, we aimed to test the hypothesis that HPC-mediated PINK1/Parkin-induced mitochondrial ubiquitination and promotes mitophagy, thus exerting neuroprotection in the hippocampal CA1 subregion against tGCI. We found that mitochondrial clearance was disturbed at the late phase of reperfusion after tGCI, which was reversed by HPC, as evidenced by the reduction of the translocase of outer mitochondrial membrane 20 homologs (TOMM20), translocase of inner mitochondrial membrane 23 (TIMM23) and heat shock protein 60 (HSP60) in CA1 after HPC. In addition, HPC further increased the ratio of LC3II/I in mitochondrial fraction and promoted the formation of mitophagosomes in CA1 neurons after tGCI. The administration of lysosome inhibitor chloroquine (CQ) intraperitoneally or mitophagy inhibitor (Mdivi-1) intracerebroventricularly abrogated HPC-induced mitochondrial turnover and neuroprotection in CA1 after tGCI. We also found that HPC activated PINK1/Parkin pathway after tGCI, as shown by the augment of mitochondrial PINK1 and Parkin and the promotion of mitochondrial ubiquitination in CA1. In addition, PINK1 or Parkin knockdown with small-interfering RNA (siRNA) suppressed the activation of PINK1/Parkin pathway and hampered mitochondrial clearance and attenuated neuroprotection induced by HPC, whereas PINK1 overexpression promoted PINK1/Parkin-mediated mitophagy and ameliorated neuronal damage in CA1 after tGCI. Taken together, the new finding in this study is that HPC-induced neuroprotection against tGCI through promoting mitophagy mediated by PINK1/Parkin-dependent pathway.


2020 ◽  
Vol 9 (1) ◽  
pp. 24-29
Author(s):  
S. V. Emel'yanchik ◽  
O. A. Karnyushko ◽  
S. M. Zimatkin

The aim of the study was to investigate the distribution and content of neuroglobin in the pyramidal neurons of the frontal and parietal cortex of white rats during simulated cholestasis.Material and methods. The study included 60 outbred white male rats weighed 200–250 g. Cholestasis was simulated by ligation of the common bile duct in the porta hepatis area (main group, n=30). Animals of the control group (n=30) were performed a false operation preserving physiological bile outflow. Sections of the frontal and parietal cortex of white rats were selected for investigation. The content and distribution of neuroglobin was detected immunohistochemically on paraffin sections using mouse monoclonal primary antibodies Anti- Neuroglobin antibody (Abcam). Cytophotometric analysis was used to perform quantitative assessment of the content of the studied molecular marker; after that statistical analysis was performed.Results. It was found that the content of neuroglobin in the pericarions of neurons of the frontal and parietal cortex modified in a wave-like mode. After ligation of the common bile duct, the content of neuroglobin significantly decreased in 2, 10 and 45 days (minimum on the 10th day) in the frontal cortex and in 90 days in the parietal cortex, and increased in 5 and 20 days of the experiment (maximum on the 20th day).Conclusion. In cholestasis, the content of neuroglobin in the pericarions of neurons of the frontal and parietal cortex modifies in waves: a decrease is observed on the 2nd, 10th, 45th day; an increase is observed on the 5th and 20th day; a recovery is observed on the 90th day.


2017 ◽  
Vol 10 (2) ◽  
pp. 137-144
Author(s):  
Natalya Alexandrovna Malkina ◽  
Alexander Alekseevich Andreev ◽  
Anton Petrovich Ostroushko

Chronic osteomyelitis is one of their complex health problems, since it accounts for up to 6% of cases in the structure of the pathology of the musculoskeletal system, relapses of the disease occur in 30%, and disability is 90% of cases.The aim of the study was to improve the results of treatment of experimental chronic osteomyelitis by applying ultrasound sanation and synthesized collagen hydrolyzate.Materials and methods. The study was carried out on 210 white rats, which were divided into 5 groups: 2 control rats and 3 experimental ones. In the 1st control group, no treatment was performed. In the 2nd control and experimental groups, the hearth was surgically sanitized. In the 1 st experimental group, the focus was performed by ultrasonic treatment. In the 2nd experimental group, the bone cavity was filled with a synthesized hydrolyzate of collagen. In the third experimental group, the combined use of ultrasound sanitation of the focus and filling it with synthesized collagen hydrolyzate was carried out. To assess the dynamics of treatment, the analysis of the general condition of animals, hematological and morphometric studies was performed.Results and their discussions.The dynamics of the general state of animals, the antioxidant defense system, the mineral metabolism, and the evaluation of the histoarchitectonics of bone tissue have been studied. It was noted that against the backdrop of the inflammatory process in chronic osteomyelitis, all the studied indicators indicate a reduced regenerative capacity. Using the developed treatment methods based on ultrasound sanitation, synthesized collagen hydrolyzate, as well as their combination, accelerated relief of inflammatory phenomena, normalization of AOS, mineral metabolism, and regenerative abilities of bone tissue were observed.Conclusions. The developed complex method of treatment based on combined application of ultrasound sanation and synthesized collagen hydrolyzate allowed to shorten the healing period of the wound defect, normalize the general condition of animals, free radical oxidation and mineral metabolism parameters, and accelerate the regenerative capabilities of bone tissue.


Author(s):  
A. D. Selin ◽  
N. A. Terekhina ◽  
G. A. Terekhin

The purpose of the survey is to experimentally study the influence of electromagnetic radiation from the decimeter range on the permeability of erythrocyte membranes. The object of the study was the blood of 80 white rats, 60 of them for three months were under the influence of electromagnetic radiation of the decimeter range. 20 animals of the control group were not exposed to electromagnetic fields. The intensity of free radical oxidation was evaluated using chemiluminescent analysis of red blood cells and blood plasma. The permeability of erythrocyte membranes and the content of reduced glutathione in blood erythrocytes were determined spectrophotometrically. A prolonged stay of animals under the influence of an electromagnetic field leads to pronounced changes in chemiluminescence indices in erythrocytes: a decrease in the maximum intensity of chemiluminescence (Imax), light sum (S), and light sum after the maximum value of chemiluminescence (Simax). Despite the increase in the content of glutathione and the chemiluminescent analysis index tg2 reflecting the antioxidant potential, there is an increase in the permeability of erythrocyte membranes under the influence of electromagnetic radiation


2007 ◽  
Vol 34 (S 2) ◽  
Author(s):  
D Siemen ◽  
Y Cheng ◽  
X Gu ◽  
P Bednarczyk ◽  
GG Haddad ◽  
...  

Author(s):  
E. K. Rakhmatullin ◽  
O. D. Sklyarov

The article presents the results of a study of the "Bisolbi" drug toxicity (powder of light ash color, poorly soluble in water). When it is mixed with water it forms a suspension of particles that settle rapidly. Values of acute drug toxicity were determined on rats. We studied groups of six animals of the same sex, as well as similar control ones. The "Bisolbi" drug was injected to white rats intragastrically, males weighing 310 ... 320 g in doses of 2500 and 2740 mg / kg. Each dose was used in six animals; distilled water (3 ml) was used for the controls. The LD50 was calculated by the probit analysis method proposed by Litchfield and Wilcoxon modified by Z. Roth. When administered orally, an atraumatic metal probe was immersed in the stomach. Within 14 days monitored the overall health status and behavior of animals, the manifestation or absence of symptoms of intoxication; noted the features of feed and water ingestion, assessed the condition of the coat, physiological functions. Then groups of experimental rats were euthanized and pathomorphologically examined. We studied the effect of "Bisolbi" with repeated introduction and on not purebred dogs. Two groups of 3-4 years of age were completed with an average initial body weight of 13.63 ... 15.11 kg. Before use, the additive was thoroughly mixed with feed. The drug was injected during 31 days at a dose of 0.5 g / kg. Dogs of the control group (three) were fed wheat flour. After 15 and 31 days in laboratory animals in order to characterize the general condition in the blood, the amount of protein, urea, glucose, creatinine, cholesterol were determined. Based on studies it was found that the drug daily application by animals, is low toxic and safe, does not provoke the development of pathological reactions. According to the Hodge and Sterner classification "Bisolbi" can be attributed to the 6th class of toxicity - relatively harmless. Accordingto GOST 12.1.007-76 LD50 of the drug is more than 151 mg / kg, but less than 5000 mg / kg it is the 3rd hazard class (moderately hazardous).


Author(s):  
L. K. Parkhomenko ◽  
◽  
L. A. Strashok ◽  
S. I. Turchina ◽  
G. V. Kosovtsova ◽  
...  

Recently, interest in the problem of free radical oxidation in biological membranes, which is directly related to both the normal functioning of cells and the occurrence, course and outcome of many pathological conditions, has increased again in clinical medicine. The aim was to determine the role and impact of antioxidant defense in boys with hypoandrogenism. The study involved 75 adolescents with hypoandrogenism aged 13–18 years, who underwent a complex of clinical and laboratory examinations. All patients were conducted complex of anthropometric research and determination of the degree of delayed puberty, laboratory and instrumental examination. Free radical oxidation was determined by the levels of malondialdehyde, conjugated dienes, carbonated proteins, superoxide dismutase and catalase in the serum, and restored glutathione and glutathione peroxidase in whole blood. Based on their determination, the coefficient of oxidative stress was calculated. Statistical processing of results was performed using parametric and nonparametric methods. The study of indicators of the free radical oxidation process found that adolescents with hypoandrogenism have multidirectional changes in the oxidation of proteins and lipids, namely: the level of conjugated dienes increases, the concentration of malondialdehyde remains at the level of the control group, and the level of carbonated proteins tends to decrease. As for the activity of antioxidant protection enzymes, a significant decrease in the level of glutathione peroxidase was detected, while the level of superoxide dismutase and catalase remained at the level of normative indicators. Oxidative stress accompanies and is one of the pathogenetic links in the formation or maintenance of the state of hypoandrogenism in boys. This requires the use of antioxidants, the complex of which must be selected individually.


Author(s):  
N.I. YAROVAN ◽  
E.N. RYZHKOVA ◽  
Y.V. KARTAMYSHEVA

Представлены результаты изучения влияния растительных адаптогенов на основе облепихи крушиновидной, боярышника обыкновенного, рябины обыкновенной и каштана конского на уровень железа при его дефиците, оксидантно-антиоксидантный статус и молочную продуктивность коров, содержащихся в условиях промышленного комплекса. Были сформированы 5 групп животных по 10 голов. Животные I (контрольной) группы получали основной рацион (ОР) II ОР измельченные семена каштана конского 50 г на 1 голову в сутки III ОР измельченные семена каштана конского 30 г высушенные плоды рябины обыкновенной 20 г на 1 голову в сутки IV ОР цельнозамороженные плоды облепихи крушиновидной 200 г на 1 голову в сутки V ОР цельнозамороженные плоды облепихи крушиновидной 130 г высушенные плоды боярышника обыкновенного 40 г на 1 голову в сутки. В опытных группах II, III, IV и V обнаружено увеличение содержания железа в сыворотке крови к 20-му дню эксперимента на 87, 78, 41 и 58, соответственно. Наблюдалось постепенное снижение уровня свободно-радикального окисления к 30-му дню опыта у коров этих групп. Уровень малонового диальдегида (МДА) снизился на 37,5, 13,4, 20 и 20, соответственно. Увеличение среднесуточного удоя отмечено у коров, получавших комплекс растительных средств из семян каштана плодов рябины (на 7,4) и плодов облепихи плодов боярышника (на 7,5).The resalts of impact studies of plant-based adaptogens (sea-buckthorn, hawthorn, mountain ash and chestnut) on serum iron level in cows, oxidative-antioxidant status and milk production of cattle contained in the industrial complex were shown. 5 groups were formed with 10 animals each: 1st control group (I) - animals received the main diet (MD) 2nd group (II) - MD chestnut seeds (50 g per 1 animal) 3rd group (III) - MD chestnut seeds/ mountain ash (30 g/20 g per 1 animal) 4th group (IV) - MD sea-buckthorn fruits (200 g per 1 animal) 5th group (V) - MD sea-buckthorn fruits/ hawthorn fruits (130 g /40 g per 1 animal). In experimental groups II, III, IV и V, an increase in the content of iron in blood serum by the 20th day of the experiment by 87, 78, 41, 58, respectively, was shown. There was also a gradual decrease in the free radical oxidation level by the 30th day of the experiment in cows of experimental groups II, III, IV и V, the malondialdehyde level (MDA) decreased by 37.5, 13.4, 20, 20 respectively compared to the initial values. The highest average daily milk production was observed in cows receiving a complex of herbal remedies from chestnut seeds mountain ash fruits (an increase by 7.4) and sea-buckthorn fruits hawthorn fruits (an increase by 7.5).


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