We have reviewed current understanding of ischemic brain damage and the main therapeutic approaches. Pathological factors affecting the survival of neurons and glial cells in the focus of ischemia are outlined: depolarization, cytotoxic and vasogenic edema, calcium overload, excitotoxicity, inflammation, free radical damage. Effective and rapid reperfusion significantly improves patient’s survival and functional outcomes, but other approaches to brain infarction treatment did not approve their effectiveness in large clinical trials. Dozens of drugs (neuroprotectors) are being studied in order to compensate isolated pathological brain ischemia pathways and to increase cellular survival, but they were ineffective in large clinical trials.
The reason for the ineffectiveness of neuroprotective drugs may be a lack of understanding of the drug targets real importance. Many drugs that have shown promising results in preclinical studies have not been studied in large clinical trials until now. Additional pathogenetic mechanisms revealed in the last decade expand our knowledge about the brain infarction and may become promising directions for the development of new therapeutic approaches.

Myocardial reperfusion syndrome is a complex set of pathological processes that occur in the heart muscle due to restoration of coronary blood flow in patients with ST-segment elevation myocardial infarction. Despite the fact that it has been known for a long time, there is still no unequivocal opinion about the predictors, and, accordingly, the risk groups for its occurrence. This prevents predicting the further course of the disease and studying the effectiveness of surgical and therapeutic methods for preventing the consequences of reperfusion in patients with ST-segment elevation myocardial infarction, which in turn significantly worsens the postoperative and long-term prognosis in this group of patients. We used the search engines such as E-lilbrary, Google Scholar and Pubmed to search for studies on this issue. The article presents research data highlighting predictors of myocardial reperfusion syndrome. In addition, the problems of verification of irreversible reperfusion injury and myocardial stunning are described.

Introduction. Typical basis of chronic cerebral ischemia in young people is small vessel disease (SVD) diagnosed by micro-focal lesions and microstructural damage of cerebral white matter (WM), reduction of fractional anisotropy (FA) in diffusion tensor MRI (DT-MRI). Previous studies showed that increased dopplerographic pulsatility and resistivity indices in middle cerebral artery (MCA PI-RI) correlated with SVD manifestations and cognitive impairment in middle-aged and elderly patients. Aim – to determine early markers and predictors of asymptomatic SVD in young and middle-aged individuals without cognitive impairment.
Materials and methods. 52 male employees of the EMERCOM, 47.3±7.6 years, without neurological or cognitive deficits were examined. Duplex scanning with MCA PI-RI calculation, MRI with WM damage assessment according to Fazekas scale, DT-MRI FA definition were completed.
Results. All those examed showed MRI signs of SVD. Two groups were formed according to Fazekas: 0 points (n-38) and 1-2 points (n-14). The 2nd group showed higher MCA PI-RI (p<0.002 and p<0.05). Multivariate logistical regression analysis showed significant correlation of PI in MCA (OR: 2.33; 95% CI: 1.13- 4.81; p=0.02) with WM lesion according to Fazekas. The FA in cognitively important tracts was lower in group 2 (p<0,001). A stepwise multiple linear regression model revealed that the strongest predictors of FA reduction were PI and RI. The values of psychomotor speed and attention span were lower in group 2.
Conclusion. MCA PI-RI are early markers of focal lesions and microstructural changes in WM and predictors of cognitive impairment in the young and middle-aged with asymptomatic SVD.

Introduction. Reperfusion-reoxygenation syndrome (RRS) after revascularization of the lower limbs in obliterating atherosclerosis of the arteries is accompanied by a violation of the oxygen transport function of the blood (OTFB) and the content of gas transmitters (GTs). Reperfusion injury affects not only the tissues of the lower limbs, but also of anatomically distant organs, which supposes that effective RRS correction is required. Aim. To study the effect of Corvitin on the OTFB parameters and the content of GT of nitrogen monoxide (NO) and hydrogen sulfide (H₂S) in the venous blood of the forearm after revascularization of the lower limb in chronic atherosclerotic occlusion of the superficial femoral artery (SFA).
Materials and methods. The study included 118 male patients. Revascularization of the lower limb was carried out by the method of loop endaterectomy from the SFA. Patients of group I (n=52) received traditional medication, 51 patients of group II additionally received Corvitin. In the blood from the vein of the elbow bend before the operation, on the 3^rd and 8^th days after it, the indices of OTFB and GTs were determined.
Results. In group I, on the 3^rd day after surgery, pO₂ increased in relation to healthy individuals by 5.2–18.5%, while pCO₂ decreased by 4.8–6.7%, depending on the stage of initial ischemia. The concentrations of NO and H₂S increased by 9.2–50.1% and 9.2–21.1%, respectively. The increase in the parameters of hyperoxemia, hypocapnemia and GT after the return of blood circulation decreases with the use of Corvitin (p˂0.05). By the end of the early postoperative period, the indicators of OTFB and GT not only return to their initial values, but also do not significantly differ from the group of healthy individuals (p˃0.05).
Conclusion. The use of Corvitin effectively corrects violations of OTFB and GT during ischemia-reperfusion of the lower limbs, which prevents tissue reperfusion damage.

Introduction. Conventionally, hemodynamic significance of carotid stenosis is characterized with an increased peak systolic velocity up to 230 cm/s, which corresponds to 70 % carotid stenosis. This does not take into account changes of cerebral hemodynamics or collateral circulation, which can be determined by assessment of blood flow distribution in precerebral arteries.
Aim – to evaluate blood flow redistribution in precerebral arteries in patients with critical carotid stenosis.
Materials and methods. 40 patients (aged 49–80 y. o.) with critical carotid stenosis were studied (13 patients had 70–79 % stenosis, 11 patients – 80–89 %, and 16 patients – 90–99 % stenosis). Flow velocity index in precerebral arteries was determined with duplex scanning (Vivid e, USA), whereas linear blood flow velocity in intracranial arteries – with transcranial Doppler (MultiDop X, Germany).
Results. In 60 % of patients, flow velocity index in ipsilateral carotid artery was reliably decreased (p<0.05). In 49 % of patients flow velocity index in contralateral carotid artery and blood flow velocity in contralateral anterior cerebral artery were reliably increased (p<0.05), as well as linear blood flow velocity in the contralateral anterior cerebral artery. Just in 39 % of patients flow velocity index in ipsilateral vertebral artery and linear blood flow velocity in ipsilateral posterior cerebral artery were increased (p<0.05). In 13 % of cases flow velocity index in the external carotid artery was increased (p<0.05).
Conclusion. Thus, critical degree of carotid stenosis does not always indicate its hemodynamic significance. Flow velocity index distribution in precerebral arteries can be used as an additional criterion for assessing hemodynamic significance of carotid stenosis and, along with other indicators, should be taken into account when choosing treatment modality.

The aim of the study was to evaluate the effect of silent myocardial ischemia on the life quality and on the frequency of occurrence and severity of depressive disorders in patients with Ischemic Heart Disease.
Materials and methods. The study involved 93 persons, including 42 practically healthy individuals and 51 patients with Ischemic Heart Disease: silent myocardial ischemia. The study included males, aged 45 to 60 years old. To assess the life quality, the Russian validated version of the Medical Outcomes Study-Short Form (SF-36) questionnaire developed by the Boston Institute of Health was used. The Hamilton Depression Rating Scale (HDRS) was used to study the psycho-emotional state of the patients. Statistical data analysis was performed using the Statistica 10.0 and Microsoft Excel 2010 software package.
Results. Role functioning (RF) was reduced by 32 % (p<0.0001), general health (GH) was reduced by 31 % (p<0.0001), and mental health was reduced (MH) by 32 % (p<0.0001), social functioning (SF) decreased by 30 % (p<0.0001) in patients with silent myocardial ischemia compared to healthy persons. Both integral indicators of life quality were also reduced in the patients with silent myocardial ischemia compared to the control group. The integral indicator «Physical component of health» for group I was 52.24 [37.4; 59.8] and for group II – 48.84 [41.08; 53.01], p<0.001. The integral indicator «Mental health component» for group I was 54.00 [51.45; 56.76] and for group II – 47.09 [30.29; 52.71], p<0.00001. Mild to moderate depression was found in 35.3 % of the patients with silent myocardial ischemia, and 15.68 % was with severe and extremely severe depression.
Conclusions. Silent myocardial ischemia decrease the life quality of patients and promotes the development of depressive states.

Introduction. Patients with Alzheimer’s disease (AD) have reduced cerebral vascular density (VD), which impairs blood flow to neurons and may contribute to progression of AD. Earlier we showed that prior adaptation to intermittent hypobaric hypoxia (IHH) prevented memory loss and degeneration of cortical neurons in rats with experimental AD (EAD).
The aim of this study was to test if IHH might prevent EAD-induced vascular rarefaction in rats.
Materials and methods. EAD was induced with bilateral injection of neurotoxic beta-amyloid peptide fragment (A) (25–35) into n. basalis magnocellularis. IHH was simulated at a 4,000 m altitude, for 4 hours a day, for 14 days. Brain blood vessels were stained by transcardiac infusion of Indian ink; brain sections were stained with 0.3 % cresyl violet by Nissle method. Vascular density was assessed in the cortex and hippocampus using the Infinity Analysis Software.
Results. In the EAD rats, VD was significantly decreased in the hippocampus (13.3±0.9 vs 17.8±1.0 in field of view, FOV, p<0.03) and in the cortex (17.3±1.5 vs 22.3±1.3 in FOV, p<0.03). AIH increased VD in the hippocampus to 27.0±3.5 in FOV (p=0.01) and in cortex to 26.0±1.1 in FOV (p<0.03). In EAD+AIH rats, VD did not differ significantly from the control rats neither in the hippocampus, nor in the cortex. AIH may stimulate angiogenesis through hypoxia inducible factor-1α-mediated expression of vascular endothelial growth factor and/or by increasing expression and activity of antioxidant enzymes.
Conclusion. One of the mechanisms of AIH beneficial effect in AD-related neurodegeneration is preserving the capability for compensatory angiogenesis in brain.

Introduction. The effectiveness of cell therapy at the stage of critical limb ischemia is insufficient for regression of clinical manifestations of the ischemic process.
Aim – to develop an experimental model of critical limb ischemia and to study the effect of the combined use of bone marrow autocells and simvastatin on the perfusion of ischemic tissues and the dynamics of the clinical picture of the ischemic process.
Materials and methods. The experimental study was carried out on 180 male Wistar rats, divided into 6 groups of 30 animals each. In the first group (intact), the level of microcirculation in the muscles of the hind limb was determined. In the second group (sham-operated), the neurovascular bundle of the thigh was isolated and the wound was sutured with a continuous suture. In the third group, chronic critical ischemia of the leg muscles was modeled by removing the femoral, popliteal, anterior and posterior tibial arteries and veins, and damage to the peripheral nerve. In the fourth group, critical ischemia of the leg muscles was treated with simvastatin, in the fifth group – with the mononuclear fraction of autologous bone marrow, in the sixth one – with simvastatin and the mononuclear fraction of autologous bone marrow. The level of microcirculation in the leg muscles was determined using laser Doppler flowmetry LDF 100C and invasive needle sensor TSD144 on days 10, 21 and 28.
Results. In the second group, a statistically insignificant decrease in the level of microcirculation was noted. In the third group, the level of regional blood flow in the ischemic muscle of the leg of rats on the 10^th day was 2.5 times, on the 21^st day – 1.7 times and on the 28^th day 1.4 times less than in the group of intact animals. At the same time, in the fourth group after the administration of simvastatin to the animals, the regional blood flow increased 1.4; 1.5 and 1.5 times; in the fifth group, with the introduction of the mononuclear fraction of the bone marrow to animals at all periods, 1.6 times; in the sixth group after the combined administration of bone marrow cells and simvastatin – 2.0; 1.8 and 1.7 times. By the end of the experiment, in the animals of the fourth and fifth groups, it was possible to stop the progression of clinical manifestations, and in animals of the sixth group, their regression was achieved.
Conclusion. The combined use of bone marrow cells and statins allows bringing the level of perfusion of ischemic tissues to normal and achieving regression of the clinical picture of the ischemic process by the end of the experiment.

Introduction. The development of an objective non-invasive method for intraoperative assessment of intestinal viability remains urgent for modern surgery. In this context, the method of laser fluorescence spectroscopy (LFS) of coenzymes of oxidative metabolism, as well as a combination of this technique with the simultaneous use of laser Doppler flowmetry (LDF) seems promising.
Materials and methods. The model of ischemia-reperfusion of the small intestine of 4 Californian Rabbits was used to study the relationship of the parameters of LFS and LDF with the histological picture. A model of intraoperative ischemia was used by temporarily clamping the trunk of the cranial mesenteric vascular bundle for 90 min, followed by intraoperative and postoperative reperfusion for 60 minutes and 24 hours, respectively. LDF and LFS data were recorded from intestine at the end of the intraoperative reperfusion period. 24 hours after the surgery, the animals were subjected to histologic evaluation of intestine ischemic changes, which were compared with the LDF and LFS data. Diagnostic value of LDF and LFS, and their combination for intraoperative assessment of intestinal viability were analyzed.
Results. A significant correlation was found between the parameters of LDF, LFS and the degree of ischemic changes according to the histological data. The method of isolated assessment of the difference in the fluorescence of reduced nicotin adenine dinucleotide (NADH) before and after ischemia-reperfusion (77.3 %) has the greatest diagnostic value. The method has the highest sensitivity with a combination of differences in LDF and LFS values before and after ischemia-reperfusion (85.7 %) (P<0.05).
Conclusions. LFS, as well as its combination with LDF, is a useful method for objective assessment of intestinal viability, which requires further research and has potential for clinical use.

Introduction. With a decrease in the oxygen content in the inhaled air, violations of the cerebral blood flow, brain ischemia occurs, which can end in an ischemic stroke.
Aim. Comparative analysis of the intensity of nitric oxide (NO) production and the copper content in the olfactory bulb tissues of the brain of male Wistar rats after modeling an ischemic stroke.
Materials and methods. Modeling of ischemic stroke by ligation at the bifurcation level of both common carotid arteries and measuring the content of NO and copper by EPR spectroscopy.
Results. The relative changes in the number of NO-containing complexes and the copper content were estimated from the integrated signal intensity of the complexes (DETC)₂-Fe²⁺-NO and (DETC)₂- Cu. A significant decrease by 47 % after 1 and 57 % after 2 days, respectively, in the NO content in the olfactory bulb of the rat brain was found after the ischemia modeling. The level of NO production in rats that underwent ischemia simulation with simultaneous intranasal administration of mesenchymal stem cells (MSCs) was also reduced by 51 % after 1 and 70 % after 2 days, respectively, after ischemia modeling. There was no significant difference in the NO content in the rats after ischemia modeling with simultaneous intranasal administration of MSCs compared to the ischemic rats. The copper content, which corresponds to the level of superoxide dismutase 1 and 3, in the rat’s olfactory bulb tended to increase after ischemia modeling and it persisted for two days of observation (an increase of 50 % in both cases). Intranasal administration of MSCs was accompanied by a significant increase in the Cu content (by 89 %) 1 day after the ischemia modeling, and 2 days later – by a decrease in its content by 36 % (compared to the control). In the control animals that were not subjected to surgical operations, no changes in the content of NO or copper were observed.
Conclusion. The experiments showed a 2-fold decrease in the NO content in the olfactory bulb of the rat brain 1 and 2 days after the ischemia modeling, and demonstrated that the intranasal administration of MSCs did not affect the intensity of NO production on the 1st and 2nd days after the brain ischemia modeling, but was accompanied by an increase in the antioxidant protection of the nervous tissue one day after ischemia.

Introduction. Increased resistance of the heart to ischemia/reperfusion (I/R) is an urgent aim of physiology, pharmacology, and cardiac surgery, since I/R injury of the heart is often the cause of cardiogenic shock and subsequent death of patients in the postoperative period.
Materials and methods. The study was carried out in male rats which were subjected to coronary artery occlusion (45 min) and reperfusion (2 h). Before coronary occlusion, early hypoxic preconditioning (HP) was modeled. The rats were subjected to six sessions of hypoxia (8 % O₂, 10 min) and reoxygenation (21 % O₂, 10 min) 30 min before coronary artery occlusion. The rats were injected with the following drugs: 1,3-dimethylthiourea (DMTM), 2-mercaptopropionyl glycine (2-MPG), deferoxamine.
Results. It was found that HP contributes to infarct size reduction by 30 %. Preliminary administration of DMTM, 2-MPG, deferoxamine eliminated the infarct-reducing effect of HP.
Conclisuon. The obtained data indicate that reactive oxygen species are involved in the cardioprotective effect of HP.