Репозиторий Университета

Background and Purpose- Ischemic stroke is one of the leading causes of disability and death. The principal goal of acute stroke treatment is the recanalization of the occluded cerebral arteries, which is, however, only effective in a very narrow time window. Therefore, neuroprotective treatments that can be combined with recanalization strategies are needed. Calcium overload is one of the major triggers of neuronal cell death. We have previously shown that capacitative Ca2+ entry, which is triggered by the depletion of intracellular calcium stores, contributes to ischemia-induced calcium influx in neurons, but the responsible Ca2+ channel is not known. Methods- Here, we have generated mice lacking the calcium channel subunit Orai2 and analyzed them in experimental stroke. Results- Orai2-deficient mice were protected from ischemic neuronal death both during acute ischemia under vessel occlusion and during ischemia/reperfusion upon successful recanalization. Calcium signals induced by calcium store depletion or oxygen/glucose deprivation were significantly diminished in Orai2-deficient neurons demonstrating that Orai2 is a central mediator of neuronal capacitative Ca2+ entry and is involved in calcium overload during ischemia. Conclusions- Our experimental data identify Orai2 as an attractive target for pharmaceutical intervention in acute stroke.

© 2019, Springer Science+Business Media, LLC, part of Springer Nature. Diallyl trisulfide (DATS) is distinguished as the most potent polysulfide isolated from garlic. The aim of our study was to investigate effects of oral administration of DATS on healthy and diabetic rats, with special attention on heart function. Rats were randomly divided into four groups: CTRL (healthy rats), DATS (healthy rats treated with DATS), DM (diabetic rats), DM + DATS (diabetic rats treated with DATS). DATS (40 mg/kg of body weight) was administered every other day for 3 weeks, at the end of which rats underwent echocardiography, glycemic measurement and redox status assessment. Isolated rat hearts were subjected to 30 min global ischemia and 60 min reperfusion, after which heart tissue was counterstain with hematoxylin and eosin and cardiac Troponin T staining (cTnT), while expression of Bax, B cell lymphoma 2 (Bcl-2), caspase-3, caspase-9 and superoxide dismutase-2 were examined in the left ventricle. DATS treatment significantly reduced blood glucose levels of diabetic rats, and improved cardiac function recovery, diminished oxidation status, attenuated cardiac remodeling and inhibited myocardial apoptosis in healthy and diabetic rats. DATS treatment causes promising cardioprotective effects on ex vivo-induced ischemia/reperfusion (I/R) injury in diabetic and healthy rat heart probably mediated by inhibited myocardial apoptosis. Moreover, appropriate DATS consumption may provide potential co-therapy or prevention of hyperglycemia and various cardiac complications in rats with DM.

© 2018, © 2018 Informa UK Limited, trading as Taylor  &  Francis Group. The aim of our study was to determine a chemical composition of methanol extract of Galium verum as well as to assess its effects on functional recovery and redox status of isolated rat heart after ischemia. Rats were divided into control and G. verum group, which included animals treated with 500 mg/kg of methanol extract of G. verum for 28 days. Parameters of heart function and oxidative stress markers were estimated. Cell morphology was evaluated by hematoxylin and eosin (HE) staining. Our results demonstrated for the first time that G. verum extract preserved cardiac contractility, systolic, and diastolic function as wells as structural damage of the heart after ischemia. Furthermore, G. verum extract modulated the activity of antioxidant enzymes and alleviated the production of pro-oxidants.

© 2018 Saint Petersburg Pasteur Institute. All rights reserved. Nowadays sepsis is grave complication of infection end the cause of death reanimation. In this survey, we would like to emphasize the importance of the control over the activation over the compliment system. It has been proved of animal model a complement one of the key role in the development of hyperactive immunity response, later resulting in violation of immunity homeostasis. Mice which had C3-/-, C4-/-deficit, aft receiving a LPS dose intraperitoneallis showed a better survival to compare with the control group of animals. There exist clinical data which confirm active participation of the compliment in the chain of the septic process. The research showed the patient affected by sepsis, had protein C3 and C4 concentration correlating which mortality at the time of diagnosis. The is chemoattractants, protein C3a and C5a, turn tube the result of complements pathway activation. The chemoattractants, provoke the extraction a big number of cytokines. Vessels permeability increase and DIC-syndrome activation wis it, multiple organ dysfunction develops. Ishemiareperfusion launch triggers aseptic inflammation, which appears decentralization and DIC-syndrome. C1-INH controls the work of classical way complement and Hemostasis System. Researchers the deficit in C1-INH animals and patients affected bay sepsis, which is proved in laboratory and clinics. The remedy C1-INH (Berinert, CSL Behring) appeared over 25 years ago and was used and therapy hereditary angioedema. For the lasted years we accumulated a considerable quantity of fasts of C1-INH use which after pathologies: heart attack, Ischemia-reperfusion injury, trauma provoked by cardiopulmonary bypass. The use of C1-INH on animal models septic in clinical research their efficacy and safety.