V. B. Koshelev

Rarefication of the arterioles and capillary network in the brain of rats with different forms of hypertension

The angioarchitecture of rat brain with deoxycorticosterone acetate (DOCA)-saline and renal forms of experimental hypertension were studied and compared with those of normotensive rats. The number of pial arteries of the third, fourth, and fifth order of branching was lower and their diameter smaller in hypertensive animals as compared with controls. In the medulla oblongata, pons, and mesencephalon the number of arterioles was lower and the total length of capillaries per unit volume was shorter in the experimental group. Rarefication of the capillary network was observed also in rats with spontaneous hypertension. Rarefication was found to begin at the earliest stage of developing hypertension. It was observed as soon as 24 hr after the ligation of the remaining kidney in rats with unilateral nephrectomy. A substantial decrease was recorded in the number of pial arteries with preserved lumens. The hypothesis that the rarefaction of the vascular net in the brain may lead to the formation of zones of ischemia is presented here.

Novel synthetic analogue of ACTH 4-10 (Semax) but not glycine prevents the enhanced nitric oxide generation in cerebral cortex of rats with incomplete global ischemia.

This work investigates whether nitric oxide production and lipid peroxidation contribute to the pathophysiology of ischemia and whether glycine and a novel Russian compound, Semax are neuroprotective via a mechanism involving the regulation nitric oxide (NO) and lipid peroxidation. In brief, nitric oxide and indices of lipid peroxidation were elevated following global ischemia. While glycine proved ineffective in reducing NO levels or ameliorating the neurological deficits following global ischemia, Semax proved to be highly effective in abating the rise in nitric oxide and restoring neurologic functioning.

Ischemic and hemorrhagic disturbances in cerebral circulation alter contractile responses of the rat middle cerebral artery

In our study, we examined middle cerebral artery (MCA) contractile responses in two animal models. After hemorrhagic disturbances in rats of Krushinsky-Molodkina strain (KMRs) a decrease in contractile responses to serotonin (5-HT) was observed. During incomplete global cerebral ischemia, MCAs had increased responsiveness to endothelin-1 (ET-1), but reduced responsiveness to serotonin. These findings suggest that cerebral circulation disorders alter cerebrovascular function possibly leading to secondary disturbances in brain circulation.

Changes in plasma membrane viscosity and hemoporphyrin conformation in erythrocyte hemoglobin under the conditions of ischemia and reperfusion of rat brain.

Hypoxia of various origin and localization is accompanied by changes in some physical and chemical properties of erythrocytes: deformability, plasma membrane viscosity, and the oxygen-binding capacity of hemoglobin [1, 4‐6]. Under the conditions of brain ischemia, these properties are studied insufficiently. After postischemic reperfusion (PIR) that restores blood circulation, the oxygen partial pressure in plasma increases, which may stimulate the generation of reactive oxygen species (ROS) and affect the erythrocyte functions. In blood plasma, Cu,Zn-superoxide dismutase (SOD) and ceruloplasmin (CP) are involved in utilization of superoxide anion radical ( ) that triggers ROS formation. In this study, changes in the viscosity of erythrocyte plasma membrane and the e 2 -binding ability of hemoporphyrin of deoxyhemoglobin were studied. SOD activity and CP level were also measured in blood plasma of rats with brain ischemia before and after brain PIR. White outbred male rats weighing 272 ± 11 g were used in experiments. The animals were divided into three groups: the sham-operated rats (the control) ( n = 10), the rats with brain ischemia ( n = 10), and the rats with postischemic brain reperfusion ( n = 7). One day before the experiment, both carotids of the anesthetized animals were underpinned with a fishing line (0.3 mm) that was later withdrawn under skin through the polyethylene tubes into the interscapular region. After one day, a one-stage complete occlusion of both carotids was induced by carotid retraction into the tubes by means of the fishing line; subsequent release of carotids led to PIR. Blood samples (3 ml of blood mixed with heparin, 10 U/ml) were taken from the jugular veins of

In vivo efficiency of Semax in global cerebral ischemia

The efficiency of neuropeptide preparation Semax was studied on an animal model of global cerebral ischemia caused by irreversible bilateral occlusion of the common carotid arteries. Semax significantly alleviated neurological deficit and slightly improved postischemic survival. These effects can be attributed to the antihypoxic and neurotrophic effects of the preparation.

Reduction of Erythrocyte Deformability in Rats with Cerebral Ischemia

Erythrocyte deformability was studied by laser interferometry in rats with cerebral ischemia. Ninety minutes after ligation of both common carotid arteries the erythrocyte deformability coefficient decreased by 11±2% in experimental group in comparison with the baseline level and by 12% in comparison with sham-operated animals and remained 16% decreased after 4 days.

Effect of short-term adaptation to hypoxia on the development of acute cerebral circulatory disorders in rats genetically predisposed to epilepsy

: The exposure of KM rats genetically predisposed to autogenic convulsive fits, to hypobaric hypoxia had a protective effect on the extension of cerebrovascular disorders in conditions of acoustic stress, reducing the severity of motor disorders and the degree of intracranial hemorrhage (subdural, subarachnoidal, intraventricular).

SEMAX INFLUENCE ON RAT CARDIOMYOCITE APOPTOTIC CELL DEATH IN IRREVERSIBLE ISCHEMIA AND ISCHEMIA-REPERFUSION

5 groups of male rats were investigated: control group; irreversible ischemia with drug and without; the animals with reperfusion after 2.5 hours of ischemia with drug and without it. Samples for light microscopy (haematoxylin-eosin and TUNEL-analysis) of the risk area (anterior wall of left ventricle) and conditionally intact myocardium (lateral wall and interventricular septum) were taken 72 hours after intervention. Semax were injected intraperitoneally at a dose of 150 mg / kg after 15 minutes and after 2 hours 15 minutes after ligation of coronary artery. The necrosis was formed in the anterior wall area both under irreversible ischemia and ischemia-reperfusion. Substantial morphological changes also developed in areas of relatively intact myocardium. These signs are accompanied by a significant increase of apoptotic index. Semax had no effects on the morphology of myocardium, but significantly reduced apoptosis of cardiomyocytes.

C-terminal Pro-Gly-Pro tripeptide in contrast to full-length neuropeptide semax exhibits no neuroprotective effect in experimental cerebral ischemia.

The C-terminal fragment Pro-Gly-Pro of semax does not modulate the development of symptoms of neurological deficiency and mortality in rats with incomplete global cerebral ischemia. Hence, previously revealed neuroprotective effects of semax are mainly determined by corticotropin ACTH4–7 fragment.

Acute Hypoxia during Organogenesis Affects Cardiac Autonomic Balance in Pregnant Rats

Changes in ECG parameters were studied in pregnant rats exposed to acute hypobaric hypoxia during the period of organogenesis (gestation days 9 to 10). Rats with low, medium, and high tolerance to hypoxia exhibited pronounced autonomic nervous system imbalance, which become apparent as a loss of correlation between various parameters of ECG signals recorded at rest and during exposure to some stress factors existing under normal conditions.