[The distribution of matrix metalloproteinases and their tissue inhibitors in the brain vascular bed exposed to chronic tobacco smoke]. / Ékspressiia matriksnykh metalloproteinaz i ikh tkanevykh ingibitorov v sosudistom rusle golovnogo mozga pri khronicheskoi intoksikatsii tabachnym dymom v éksperimente.

AIM: To study the distribution of MMP-2 and MMP-9 and their inhibitors (TIMP-2 and TIMP-1 respectively) in the brain vascular bed of rats exposed to chronic tobacco smoke. MATERIAL AND METHODS: Localization and expression of MMP-2, MMP-9, TIMP-2 and TIMP-1 in the pial branches (I-V order vessels), intracerebral arteries and capillaries of rats exposed to tobacco smoke were studied for 36 weeks. The level of enzymatic activity was assessed by the relative quantity of enzymopositive arteries and amount of fragments per 1 mm2 and rate of immunohistochemical reaction. Specific capillary density per mm2 of brain tissue and optical density of the immunohistochemical product were calculated. RESULTS: MMP-2 and TIMP-2 were found in all segments of the arterial course in control animals. In rats exposed to tobacco smoking, the expression of MMP-2 increased only in intracerebral arteries and capillaries while TIMP-2 level decreased. MMP-9 and TIMP-1 were noted only in single vessels, mainly small pial and intracerebral arteries, in intact animals. In rats exposed to tobacco smoke, MMP-9 expression significantly increased in all segments of the arterial course whereas the increase in TIMP-1 was observed mainly in large pial arteries. CONCLUSION: In physiological conditions, the dynamic balance between MMP-2 and TIMP-2 maintains basic tissue metabolism. Products of tobacco combustion are inductors of the inducible MMP-9 which promotes morphofunctional changes. The imbalance in MMP-9 - TIMP-1 system causes the degradation of extracellular matrix in different segments of the brain arterial course promoting the development of cerebral dysfunction.

Dynamics of Distribution of Capillaries with Matrix Metalloproteinase-2 and Its Tissue Inhibitor in Rat Brain during Development of Experimental Hypertension.

The capillaries containing MMP-2 and its tissue inhibitor TIMP-2 were examined in cerebral cortex and white matter obtained from intact Wistar rats (n=5) and the rats with progressing experimental renovascular hypertension (n=35). In hypertensive rats, the changes in intensity of the immunohistochemical reaction and in the density of capillaries expressing TIMP-2 significantly differed from the corresponding values in MMP-2-positive capillaries, which resulted in pronounced deviation of MMP-2/TIMP-2 index from the control level (especially in cerebral cortex) probably attesting to enhanced risk of complications in cases with arterial hypertension.

[The cellular and molecular mechanisms of angiogenesis regulation in the brain]. / Kletochno-molekuliarnye mekhanizmy reguliatsii angiogeneza v golovnom mozge.

This review presents the data on cellular and molecular mechanisms of angiogenesis regulation linked to the vascular epithelium. According to current conceptions, activated endothelial cells and their predecessors (progenitor cells) are involved in the regulation of angiogenesis. These cells synthesize angiogenic molecules differing by the chemical structure and mechanism of biological effect and allowing a direct or indirect control over each stage of angiogenesis. Both the excess and insufficient angiogenesis can lead to fast and irreversible changes in nervous tissue under certain conditions. For this reason, the balance in the system of molecular stimulators and inhibitors of angiogenesis is especially important for brain function. Without adequate reperfusion of an affected brain area the post-stroke neuroreparation, which can be provided with timely stimulation of angiogenesis, is unattainable and the intensification of this process in tumors, on the contrary, has adverse consequences. Growth of a tumor and its metastatic spread are substantially associated with an increase in the level of tumor tissue vascularization, and blocking angiogenesis is often the only productive way to limit the growth of a tumor. However our knowledge of mechanisms of angiogenesis regulation in the brain on the cellular and molecular level in physiological and pathological conditions is still insufficient, and, therefore, the influence of angiogenic factors on tissue targets do not always cause the expected effects.

Age-Specific Characteristics of CO-Mediated Reaction of the Pial Arteries of Various Diameters in Rats.

First-fourth order pial branches of the median cerebral artery were studied by biomicroscopy in male Wistar rats aged 1 and 12 months. Irrespective of age, CO-mediated mechanisms are involved in the regulation of the basal tone of pial vessels of various diameters (more so of arteries with well-developed muscular tunic). Injection of hemin confirmed that endogenous production of CO maintained vasodilatation and this effect was most pronounced in large pial branches of young animals, while zinc protoporphyrin IX blocked this effect in all cases. On the other hand, zinc IX protoporphyrin did not modify NO-mediated reaction caused by injection of L-arginine, while hemin compensated (though not completely) vasoconstriction induced by NO synthase blocker L-NAME. In contrast to NO, the effect of CO on blood vessels was not so rapid and potent, but more lasting. Other targets for CO were arteries with well-developed muscular tunic, while targets for NO were small vessels. The vasomotor effects of both gas transmitters were more pronounced in young animals.

ENDOTELIAL-DEPENDENT OF THE REGULATION OF ANGIOGENESIS.

The review presents cellular and molecular mechanisms regulating angiogenesis. In response to the angiogenesis inducers impact the activated endothelial cells and their precursors (progenitor cells) synthesize and produce angiogenic molecule that differ by chemical origin and biological functions but all of them enable these cells to influence both directly and indirectly on new vessels growth. Among the great number of angiogenic molecules the scientists hold interests in the following: the set of vascular endothelial growth factors, the set of the fibroblast growth, transforming growth factor, tumor necrosis factor and some other soluble polypeptides which occurred to be an effective regulators of angiogenesis. However, despite the evident achievements in studies of cellular and molecular mechanisms of angiogenesis it is still difficult to control this process. Therefore the main goal of the study was to review endothelial-dependent factors and mechanisms of capillary vessels growth regulation.

[The histochemical characteristics of the capillaries in the mammalian endometrium]. / Gistokhimicheskaia kharakteristika kapilliarov éndometriia mlekopitaiushchikh.

Histochemical methods (alkaline phosphatase, magnesium dependent adenosine triphosphatase (ATPase) and butyryl cholinesterase) revealed specific differences in the uterine endometrium capillary bed organization. The most informative values of capillary specific differences are indexes of alkaline phosphatase and magnesium dependent ATPase activity along with the microvessels total length. This demonstrates the peculiarities of transcapillary exchange in human and in animals studied.

[Functional morphology of capillary bed of the uterus after administration of synestrol]. / Funktsional'naia morfologiia kapilliarnogo rusla matki posle vvedeniia sinestrola.

The capillary vessels of rats uterus were examined. The animals who received 0.2% solution were examined 1, 3, 5, 10, 20, 30, 60 days after the last injection. As a marker for capillary vessels the histochemical method for finding the Mg++ adenosine triphosphatase was used. The studies have found prominent qualitative and quantitative changes (activity of enzyme, length and diameter of capillaries) not less than for two months after the last injection of the solution. Particularly prominent changes were found in endometrium between 10-20 days of the restorative period.

[The functional morphology of the uterine capillary bed after synestrol administration]. / Funktsional'naia morfologiia kapilliarnogo rusla matki posle vvedeniia sinestrola.

The capillary vessels of rats uterus was examined which were receiving for 7 days 0.2% solution of synoestrol i/m (2.0 mg per 1 kg of body weight). The animals were examined 1, 3, 5, 10, 20, 30, 60 days after the last injection of the solution. As the marker for the capillary vessels the histochemical method for finding the Mg2(+)-adenosintriphosphatase was used. The investigations have found prominent qualitative and quantitative changes (activity of enzyme, length and diameter of capillaries) not less than for two months after the last injection of the solution. Particularly prominent changes were found in endometrium between 10-20 days of the restorative period.