Maria Ulanova

THE EXPERIMENTAL STUDY OF STRESS-RELATED PATHOLOGICAL CHANGES IN CEREBRAL VENOUS BLOOD FLOW IN NEWBORN RATS ASSESSED BY DOCT

In experiments on newborn rats with stress-related intracranial hemorrhage (ICH) using Doppler optical coherence tomography (DOCT) we have shown that latent stage of ICH (4 h after stress) is characterized by decrease of venous blood outflow and the loss of sensitivity of sagittal vein to vasoconstrictor effect of adrenaline. The incidence of ICH (24 h after stress) was accompanied by progression of early pathological changes in cerebral venous blood flow (CVBF) and development of venous insufficiency. Taking into consideration of this fact, we suggest that the suppression of CVBF related to the severity to the deleterious effect of stress on the brain hemodynamics in newborn rats. These facts allow us to conclude that the venous insufficiency with the loss of vasoconstrictor response to adrenaline is an informative and sensitive component of pattern of CVBF that can be important diagnostic criteria of risk of ICH development in newborns.

Optical monitoring of stress-related changes in the brain tissues and vessels associated with hemorrhagic stroke in newborn rats

Stress is a major factor for a risk of cerebrovascular catastrophes. Studying of mechanisms underlying stress-related brain-injures in neonates is crucial for development of strategy to prevent of neonatal stroke. Here, using a model of sound-stress-induced intracranial hemorrhages in newborn rats and optical methods, we found that cerebral veins are more sensitive to the deleterious effect of stress than arteries and microvessels. The development of venous insufficiency with decreased blood outflow from the brain accompanied by hypoxia, reduction of complexity of venous blood flow and high production of beta-arrestin-1 are possible mechanisms responsible for a risk of neonatal hemorrhagic stroke.

Photodynamic opening of blood-brain barrier

Photodynamic treatment (PDT) causes a significant increase in the permeability of the blood-brain barrier (BBB) in healthy mice. Using different doses of laser radiation (635 nm, 10-40 J/cm2) and photosensitizer (5-aminolevulinic acid - 5-ALA, 20 and 80 mg/kg, i.v.), we found that the optimal PDT for the reversible opening of the BBB is 15 J/cm2 and 5-ALA, 20 mg/kg, exhibiting brain tissues recovery 3 days after PDT. Further increases in the laser radiation or 5-ALA doses have no amplifying effect on the BBB permeability, but are associated with severe damage of brain tissues. These results can be an informative platform for further studies of new strategies in brain drug delivery and for better understanding of mechanisms underlying cerebrovascular effects of PDT-related fluorescence guided resection of brain tumor.

Analysis of cerebral vessels dynamics using experimental data with missed segments

Physiological signals often contain various bad segments that occur due to artifacts, failures of the recording equipment or varying experimental conditions. The related experimental data need to be preprocessed to avoid such parts of recordings. In the case of few bad segments, they can simply be removed from the signal and its analysis is further performed. However, when there are many extracted segments, the internal structure of the analyzed physiological process may be destroyed, and it is unclear whether such signal can be used in diagnostic-related studies. In this paper we address this problem for the case of cerebral vessels dynamics. We perform analysis of simulated data in order to reveal general features of quantifying scaling features of complex signals with distinct correlation properties and show that the effects of data loss are significantly different for experimental data with long-range correlations and anti-correlations. We conclude that the cerebral vessels dynamics is significantly less sensitive to missed data fragments as compared with signals with anti-correlated statistics.

Intravital molecular tagging velocimetry of cerebral blood flow using Evans Blue

The effects of light-driven enhancement of Evans Blue dye complexes with blood plasma proteins were observed for the first time, both in vitro and in vivo. The possible background of the effect concerns the photochemical cis-trans isomerization of the azo dye molecules. The effect was induced in the solution with a red laser with a wavelength of 638 nm, which corresponds to the peak of the dye absorption. The lifetime of the enhanced fluorescence is approximately 1 second and enables its use as an optically tagged molecular flow tracer for blood flow velocity measurements. Utilizing the effect, we performed for the first time the intravital molecular tagging velocimetry of the blood velocity in blood vessels in a living animal. The results of the measurements of the blood flow velocities in the cerebral veins of a group of healthy mice are presented.

Characterization of vascular dynamics based on experimental recordings with extreme data loss

The presence of artifacts complicates analysis of physiological systems based on experimental time series. Aiming to increase the signal-to-noise ratio and to improve characterization of the system’s state, bad segments are simply removed from the experimental recording, and the latter may change correlation and other properties of the resulting dataset. Here we illustrate that in the case of positively correlated processes being typical for vascular dynamics, the authentic characterization of the system’s dynamics can be provided even under the condition of extreme data loss. Based on the cerebral blood flow (CBF) dynamics acquired with the laser speckle contrast imaging (LSCI) and the multiresolution analysis, we show insensitive changes of measures quantifying the system’s state with the amount of missed data for both, macro- and microcerebral circulation. We also demonstrate that these results do not significantly depend on the selected basic wavelet and the resolution level.

Laser-induced generation of singlet oxygen: new strategies in the treatment of brain tumor

Here we show the photodynamics (PD)-induced opening of the blood-brain barrier in dependence on different light doses and concentrations of photosensitizer that is important for correction of PD-related fluorescence guided resection of brain tumor.

Stress plays provoking role in hypertension-related stroke: injuries of blood-brain barrier function

Chronic hypertension itself does not cause stroke but significantly decreases the resistant to stroke induced by stress due to exhausting of adaptive capacity of cerebral endothelium and decrease resistance of blood-brain barrier to stress.

Characterization of cerebral blood flow dynamics with multiscale entropy

Based on the laser speckle contrast imaging (LSCI) and the multiscale entropy (MSE), we study in this work the blood flow dynamics at the levels of cerebral veins and the surrounding network of microcerebral vessels. We discuss how the phenylephrine-related acute peripheral hypertension is reflected in the cerebral circulation and show that the observed changes are scale-dependent, and they are significantly more pronounced in microcerebral vessels, while the macrocerebral dynamics does not demonstrate authentic inter-group distinctions. We also consider the permeability of blood–brain barrier (BBB) and study its opening caused by sound exposure. We show that alterations associated with the BBB opening can be revealed by the analysis of blood flow at the level of macrocerebral vessels.

The sex differences in nature of vascular endothelial stress: nitrergic mechanisms

Here we studied the role of nitric oxide in cardiovascular regulation in male and female hypertensive rats under normal and stress conditions. We found that the severity of hypertension in females was lower than in males. Hypertensive females demonstrated more favorable pattern of cardiovascular responses to stress. Nitric oxide blockade by NG-nitro-L-arginine methyl ester (L-NAME) increased the mean arterial pressure and decreased the heart rate more effectively in females than in males. During stress, L-NAME modified the stress-induced cardiovascular responses more significantly in female compared with male groups. Our data show that hypertensive females demonstrated the more effective nitric oxide control of cardiovascular activity under normal and especially stress conditions than male groups. This sex differences may be important mechanism underlying greater in females vs. males stress-resistance of cardiovascular system and hypertension formation.