scholarly journals EARLY AND REMOTE RESPONSE OF HIF-1Α PROTEIN IN THE HIPPOCAMPUS FIELDS TO ISCHEMIA-REPERFUSION IN RATS WITH DIABETES MELLITUS

2021 ◽  
Vol 9 (1) ◽  
pp. 101-106
Author(s):  
O.M. Nika ◽  
O.V. Zaliavska ◽  
O.V. Kaushanska

The role of the transcription factor Hif-1α in pathogenesis of hypoxic lesions and diabetes mellitus (DM) has been confirmed, though molecular mechanisms underlying dysfunctions of the factor in the association of DM with ischemic-reperfusion lesion of the brain remain unknown. Objective: the investigation of Hif-1α protein content in the neurons of the hippocampus fields of rats with experimental DM in the dynamics of ischemic-reperfusion lesion of the brain. The study was conducted on 60 6-month rats with DM simulated at the age of 2 months by means of a single administration of streptozotocin (60 mg/kg of the body weight) (Sigma, USA). Disorders of the cerebral circulation were simulated by means of occlusion of both carotid arteries for 20 minutes. The content of Hif1-α protein was determined by means of fluoroimmunoassay after 20-minute ischemia with one hour reperfusion, and on the 12th day of the post-ischemic period in the hippocampus fields: СА1, СА2, СА3, СА4. In rats without DM 20-minute ischemia with one hour reperfusion increases the content of Hif-1α protein in all the hippocampus fields. On the 12th day of ischemic-reperfusion period in СА2-СА4 hippocampus fields the values of certain examined activity indices of the transcription factor Hif-1α continue to increase, and in СА1 field they are normalized or come closer to the values of animals from the control group. In rats with DM at the early post-ischemic period changes of Hif-1α protein content are lacking in СА1 field, the signs of its reduced activity are found in СА2 field, in СА3 field they are limited by the response of one index, and in СА4 field they are similar to those of the control rats under the experimental conditions. On the 12th day of ischemic-reperfusion period all the activity indices of the transcription factor Hif-1α increase in СА1 filed. They are higher than the corresponding indices in animals from the control group by absolute values under similar experimental conditions; changes of the examined parameters are limited in СА2 and СА3 fields in comparison with those from the control group; the parameters, which increased in the control group of animals, decreased in СА4 field. DM restricts Hif-1α protein response to ischemia-reperfusion in the neurons of СА1-СА3 field at the early ischemic-reperfusion period and in the neurons of СА2-СА4 fields — on the 12th day of the observation.

2021 ◽  
Vol 11 (7) ◽  
pp. 288-297
Author(s):  
S. Tkachuk ◽  
O. Tkachuk ◽  
M. Povar ◽  
O. Yasinska ◽  
O. Denysenko

Introduction. The imbalance in the protease-antiprotease system is an integral part of the pathogenesis of acute disorder of cerebrovascular circulation and diabetes mellitus (DM), but its manifestations in the complication of diabetes by ischemia-reperfusion of the brain have not been investigated yet. The objective of the work – to study the dynamics of carotid ischemia-reperfusion effect on the proteo- and fibrinolytic activity in brain structures of rats with experimental DM. Rats with the four-month streptozotocin DM were modeled bilateral carotene ischemia during 20 minutes. In homogenates of brain structures, indicators of proteo- fibrinolytic activity were determined after 1 hour from the beginning of reperfusion and during the 12th day of the post-ischemic period. In the absence of DM, the proteolytic activity of all or individual indicators il increased in both periods of the post-ischemic period in the cortex of the frontal and occipital lobes, the fields of hippocampus CA2 and CA3, and during the 12th day in the field CA1. Results. In rats with diabetes, in all brain structures, there are no changes in the lysis of azo-albumin and azo-casein in both terms of observation and lysis of collagen progressively decreases. In rats without DM in the cortex of the studied particles, fields of the hippocampus CA1 and CA2, all or separate indices of fibrinolytic activity are increased in both periods of the post-ischemic period, in the field CA3 – all indices at the 12th day. In the presence of diabetes in the cortex of both studied lobes and the field CA1, the fibrinolytic activity decreases in the late post-ischemic period, in the fields of CA2 and CA3 – during both observation periods. Conclusion. In the brain structures under investigation at both time intervals, the DM eliminates the reaction of low and high molecular weight proteins to the ischemia-reperfusion and suppresses fibrinolytic activity.


2018 ◽  
Vol 25 (1) ◽  
Author(s):  
O. Tkachuk ◽  
M. Povar

The imbalance in the protease-antiprotease system is an integral part of the pathogenesis of acute disorder of cerebrovascular circulation and diabetes mellitus (DM), but its manifestations in the complication of diabetes by ischemia-reperfusion of the brain have not been investigated yet.The objective of the work – is to study the dynamics of carotid ischemia-reperfusion effect on the proteo- and fibrinolytic activity in brain structures of rats with experimental DM.Rats with the four-month streptozotocin DM were modeled bilateral carotene ischemia during 20 minutes. In homogenates of brain structures, indicators of proteo- fibrinolytic activity were determined after 1 hour from the beginning of reperfusion and during the 12th day of the post-ischemic period.In the absence of DM, the proteolytic activity of all or individual indicators is increased in both periods of the post-ischemic period in the cortex of the frontal and occipital lobes, the fields of hippocampus CA2 and CA3, and during the 12th day in the field CA1. In rats with diabetes, in all brain structures, there are no changes in the lysis of azo-albumin and azo-casein in both terms of observation and lysis of collagen progressively decreases.In rats without DM in the cortex of the studied particles, fields of the hippocampus CA1 and CA2, all or separate indices of fibrinolytic activity are increased in both periods of the post-ischemic period, in the field CA3 – all indices at the 12th day. In the presence of diabetes in the cortex of both studied lobes and the field CA1, the fibrinolytic activity decreases in the late post-ischemic period, in the fields of CA2 and CA3 – during both observation periods.Conclusion. In the brain structures under investigation at both time intervals, the DM eliminates the reaction of low and high molecular weight proteins to the ischemia-reperfusion and suppresses fibrinolytic activity. 


2021 ◽  
pp. 24-30
Author(s):  
Nataliya Volotovska

The use of hemostatic tourniquet is a proved means of primary care. However, systemic disorders, as well as ultrastructural, in the area of compression can significantly worsen the condition of the injured organism. The aim. Estimation of catalase level in rats’ liver on the background of modifications of ischemic-reperfusion syndrome to know the severest pathogenic combination for organism. Materials and methods. 260 white adult male rats were divided into 5 groups: control (KG), EG1 – simulation of isolated ischemia-reperfusion syndrome (IRS) of the limb, EG2 – simulation of isolated volumetric blood loss, EG3 – combination of IRS of the limb with blood loss, EG4 – simulation of isolated mechanical injury of the thigh, EG5 – combination of IRS of the limb and mechanical injury. The variability of catalase level in liver was analyzed. Results. It was found that each of the experimental interventions has led to changes of catalase activity in the liver. The most expressed pathological expressions were observed on the 3rd after interventions, when the studied index in EG3 was lower than in EG1 and EG2 in 6,2 times and by 33,1 %. On the 7th day catalase activity in EG3 was in 9,4 times and by 44,5 % times lower than in EG1 and in EG2 data concordantly. The combination of limb ischemia-reperfusion with blood loss in EG3 led to exhausting of liver antioxydant enzyme catalase in the most critical posttraumatic period (day 3). The same, but less significant effect was registered in the group of combination of mechanical trauma with ischemia-reperfusion in EG5. This proved the role of the tourniquet as a factor that complicated the course of traumatic disease due to ischemic reperfusion. Conclusions. In this experiment, founded risk factors of combination of ischemia-reperfusion with heavy blood loss emphasized the importance and particular attention on such widespread method of bleeding tratment, as the imposition of a tourniquet, as in our experiment it triggered risk factors of ischemia-reperfusion. It was shown katalase activity depression respectively to the periods of increasing of lipid peroxydation. There was peculiarity, that on the base of isolated IRS catalase activity was increased in 2,5 times comparely to control group, whereas the hardest depression of it was found on the background of IRS, combined with blood loss – catalase activity was lower, comparely to KG – in 2,5 times. The importance of understanding the suppression of hepatocytes’ antyoxydants is great, as it might help in prevention the development of liver failure or hepatorenal syndrome on the background of limb ischemia-reperfusion.


Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Tomoyuki Iwai ◽  
Shin Nakayama

Introduction: Cerebral edema following cardiac arrest and cardiopulmonary resuscitation (CA/CPR) is associated with unfavorable neurologic outcome. The Na + -K + -2Cl - water cotransporter NKCC1 is suspected to be a critical mediator of edema formation after ischemia. It is reported that β1 adrenoreceptor antagonists protect neurons following brain ischemia in rodents. β1 adrenoreceptor antagonists inhibit the Na + -K + -ATPase, which can inhibit driving force of NKCC1 that theoretically reduces cerebral edema following ischemia-reperfusion injury. In this study, we examined whether landiolol, a selective β1 adrenoreceptor antagonist, attenuates cerebral edema following CA/CPR. Methods: Isoflurane-anesthetized adult male mice (C57BL/6J, 25-30g) were randomized into landiolol group or control group. After 7-min CA followed by CPR, landiolol (0.5ml, 830μg/ml) was administered by continuous infusion intravenously for 4 hours. Animals in control group were given normal saline (0.5ml) in the same manner. Twenty-four hours after CA/CPR, the brain was removed to assess brain water content using wet-to-dry method. The primary outcome was measurement of the brain water content. Heart rate and arterial blood pressure were recorded. Measured parameters were analyzed by one-way ANOVA with post hoc Tukey-Kramer test using SPSS® statistics 25. Differences were considered statistically significant at a P value < 0.05. Results: Brain water contents was increased in control group mice after CA/CPR (n=10) compared with those in sham operated mice (n=5) (79.5±0.85% vs 78.3±0.14%, P=0.003). Compared with control group, landiolol treatment significantly reduced brain water content in mice subjected to CA/CPR (n=12) (78.9±0.51% vs 79.5±0.85%, P=0.04). Conclusion: Landiolol attenuated brain edema following CA/CPR. These results may suggest selective β1-blocker could be alternative treatment for neuroprotection in patients who suffered CA/CPR.


2021 ◽  
Vol 6 (15) ◽  
pp. 45-51
Author(s):  
Ayşe Köse Vuruşkan ◽  
Nur ELAGÜL ◽  
Tansel SAPMAZ ◽  
Sude TOPKARAOĞLU

Aim: We aimed to investigate how bilateral renal ischemia-reperfusion (I/R) damage affects the ovaries as a distant organ and the effects of melatonin (MEL), curcumin (CUR) and melatonin+curcumin (MEL+CUR) treatments on I/R damage. Material and Method: 42 female Wistar rats were used in the study. Rats were divided into 6 groups and study was designed as follows: Control group (G1) – opening and closing the abdomen only (sham surgery group) –, I/R group (G2) – 45 min ischemia followed by 2 h reperfusion –, I/R+MEL group (G3) – 45 min ischemia, intraperitoneal (i.p) 20 mg/kg MEL injection 5 min before reperfusion, followed by 2 h reperfusion –, I/R+CUR group (G4) – 45 min ischemia, 5 min before reperfusion i.p 200 mg/kg CUR injection and then 2 hours reperfusion –, I/R+MEL+CUR group (G5) – 45 min ischemia, 5 min before reperfusion i.p 20 mg/kg MEL and 200 mg/kg CUR injection, followed by 2 hours reperfusion –. At the end of the reperfusion period, the rats were sacrificed. Right ovaries were removed from the peritoneum and fixed. After fixation and follow-up, tissue sections were stained with hematoxylin&eosin (H&E), Periodic acid-Schiff (PAS)+Hematoxylin (PAS+H) and Masson’s trichrome stains. Pathological changes were scored and statistically evaluated. Results: Compared to the control group, there was a decrease in hemorrhage, vascular congestion, follicular degeneration, inflammation, interstitial edema, vasodilation and growing follicle numbers in all groups; these changes were severe in the G2 group; Mild to moderate severity was observed in the G3, G4 and G5 groups. Conclusion: Renal I/R damage significantly affects the ovaries histopathologically. MEL, CUR, and MEL+CUR partially preserve the histological structure, but MEL treatment seems to be more effective than CUR treatment.


2017 ◽  
Vol 42 (9) ◽  
pp. 901-908 ◽  
Author(s):  
Thibault Le Roux-Mallouf ◽  
Florence Vibert ◽  
Stéphane Doutreleau ◽  
Samuel Verges

Nitric oxide (NO) is implicated in vasomotor control mechanisms altering the diameter of the vessels under various physiological and pathological conditions. There are 2 main NO production pathways, 1 NO synthase (NOS) independent (nitrate–nitrite–NO) and the other is NOS dependent (citrulline–arginine–NO). The objective of the study was to evaluate the effect of acute nitrate and citrulline supplementation on post-ischemic vascular response in healthy subjects. Fourteen subjects performed 2-leg vascular occlusion tests, 3 days apart. They were randomly assigned to consume a drink containing 1200 mg (19.4 mmol) of nitrate and 6 g of citrulline (N+C) or a placebo (Pl). Changes in total hemoglobin (Hbtot) and oxyhemoglobin (HbO2) concentrations were recorded by near-infrared spectroscopy on the thigh and calf muscles. No differences between N+C and Pl were observed during the ischemic period. Hbtot increased to a larger extent during the reperfusion period for the thigh (e.g., area under the curve, 821 ± 324 vs. 627 ± 381 mmol·s−1, p = 0.003) and the calf (515 ± 285 vs. 400 ± 275 mmol·s−1, p = 0.029) in the N+C versus Pl conditions. Similar results were found regarding HbO2 for the thigh (e.g., area under the curve, 842 ± 502 vs. 770 ± 491 mmol·s−1, p = 0.077) and the calf (968 ± 536 vs. 865 ± 275 mmol·s−1, p = 0.075). The larger postocclusive Hbtot and HbO2 responses observed after N+C intake suggests a greater post-ischemic vasodilation, which may be due to increased NO availability, via the activation of the 2 main NO production pathways.


1993 ◽  
Vol 265 (2) ◽  
pp. H642-H648 ◽  
Author(s):  
H. Theilen ◽  
H. Schrock ◽  
W. Kuschinsky

Previous studies have shown a complete plasma perfusion of all capillaries in the rat brain under normal physiological conditions. This raises the question under which experimental conditions nonperfused capillaries may show up in the brain. Two experimental models were investigated in rats. 1) Reduced cerebral blood flow (CBF) during incomplete forebrain ischemia: hemorrhagic hypotension was maintained for 30 min at a mean arterial blood pressure of 41 mmHg. During the final 5 min of hypotension both carotid arteries were ligated. 2) Reperfusion after incomplete forebrain ischemia: reperfusion lasted for 4 h after either 15 or 30 min of incomplete forebrain ischemia. Under both experimental conditions, the density of the existing as well as the plasma-perfused brain capillary network was quantified using fluorescent double staining. Local CBF was measured during incomplete forebrain ischemia using the quantitative autoradiographic 4-iodo-[N-methyl-14C]antipyrine technique. The results showed a decrease in CBF during incomplete forebrain ischemia, which amounted up to 94%. Whereas normotensive control animals showed a complete staining of all capillaries within 5 s after the intravenous injection of Evans blue, this period of time was increased to 10 s during incomplete forebrain ischemia, indicating a delayed capillary perfusion. Four hours of reperfusion after 15 min of incomplete forebrain ischemia resulted in a complete capillary staining, whereas reperfusion after 30 min of ischemia was followed by intracerebral bleedings and a few nonperfused capillary areas (circulation time of Evans blue: 10 s).(ABSTRACT TRUNCATED AT 250 WORDS)


2020 ◽  
Author(s):  
Radnaa Gochoo ◽  
Oyuntsetseg Namsrai ◽  
Dagvatseren Begzsuren ◽  
Bat-Erdene Jargalsaikhan ◽  
Chimedragchaa Chimedtseren

Abstract Background Stroke is leading cause of morbidity and mortality in worldwide. Despite valuable progresses in understanding neurological deficits after stroke, its therapeutic options are remaining limited. We aimed to study the neuroprotective effect of musk on cerebral ischemia/reperfusion injury model rats.Methods:In our experiment, we used 180 whore meal breed Wistar rats which weigh 180-220 g and divided these rats into 50 mg/kg of musk, 100 mg/kg of musk, 10 mg/kg of nimodipine, the ischemic-reperfusion groups by filling the midriff of the brain and take the drugs for 7 days in each group. Cerebral ischemia/reperfusion was induced in rats by temporary middle cerebral artery occlusion-reperfusion (MCAO/R) followed by treatment with musk at 50 mg/kg and 100 mg/kg doses. On days 1, 3 and 7 after MCAO/R, TGF-β, BDNF, TrkB and NGF mRNA expressions in the rat brain tissue were quantitatively analyzed using RT-PCR.Results:Musk 50 and 100 mg/kg treated groups brain stroke size were significantly decreased compared with the experimental group at 1, 3 and 7 days. Moreover, brain BDNF, TrkB, NGF and TGF-β mRNA express were not significant difference between experimental and control group. Also 3rd and 7th day, the data indicate that Musk 50 and 100 mg/kg were significantly (p<0,05) effective increasing rats brain BDNF, TrkB, NGF and TGF- β mRNA express in rats with ischemic stroke induced by MCAO/R. Conclusions: The 50 and 100 mg/kg doses of musk lead to increase neuro-protective factors BDNF, TRkB, NGF and TGF- β expression of mRNA in ischemic-reperfusion rat model. It implies that the Mongolian musk supports the neurogenesis of neuronal cell.


2020 ◽  
Vol 26 (2) ◽  
pp. 5-11
Author(s):  
T.O. Veresiuk ◽  
P.R. Selskyy ◽  
A.T. Televiak

The ischemic-reperfusion lesion is a complex multifactorial damage of the primary ischemic tissues as a result of restoration of the arterial blood circulation in them, which is accompanied by local morpho-functional reorganization of the vascular bed of the hind limbs of the rats. One of the promising means in the treatment and prevention of the reperfusion disorders is a carbacetam, which smooths the phenomena of hypo- and hyperperfusion in the post-ischemic period. The aim of the study was to established the manifestations of the morpho-functional remodeling of the vascular bed of the hind limbs of the rats in ischemia-reperfusion and under conditions of correction with carbacetam. Histological examination of the vascular bed of the hind limbs of 30 rats under conditions of ischemia-reperfusion (group I) and 30 rats in the simulation of ischemia-reperfusion, which in the post-ischemic period administered carbacetam once a day (5 mg/kg) for 14 days (group II) were done. There were 6 intact animals in the control group. Simulation of ischemia was performed by applying SWAT rubber tourniquets on the hind limbs for 2 hours, and reperfusion – by removing of the tourniquet. The animals of the experimental groups were divided into 5 subgroups with reperfusion terms after 1, 2 hours and 1 day, as well as after 7 and 14 days. Histological examination was performed according to generally accepted methods. The vascular bed in the middle third of the thigh and the shin below the tourniquet was examined using a Bresser Trino Researcher 40x–1000x microscope. Analyzing of the obtained results, was established that after 1 hour of the reperfusion the histological changes became a systemic, and after 1 day it were more significant. It should be noted that the thickness of the vessel walls increased, and the elastic membranes were partially eligned, thinned and torned. The stepwise clarity of the arterials walls structure was lost. The edema acquired a total nature. The histological examination of the vessels after 7 days revealed that the swelling of the walls decreased and the condition of the elastic frame was improved. There was a proliferation of collagen fibers in the adventitia, which was a response to ischemic effects. It is noted that after 14 days in all wall membranes the proliferative activity of fiboblasts was remained. Under the conditions of the correction with the carbacetam after 2 hours, the structural positive dynamics became more pronounced and increased to a maximum level after 7 days of the experiment. The number of the modified and exfoliated endothelial cells decreased, and the condition of smooth myocytes increased. Histologically, the gradual restoration of endothelial coverage of the intima was established. As follows, ischemia and reperfusion cause vascular remodeling after 1 hour with a peak of the manifestations after 1 day of the reperfusion, which includes edematous syndrome, dystrophic-degenerative changes with an inflammatory response to the damage, and in the late reperfusion period increased a fibroblasts activity. Gradual return of morphological changes occurs after 14 days of the experiment. Under the conditions of correction, the acceleration of the remodeling with stabilization of the process and the most possible structural restoration after 7 days of the study was noted.


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