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/cm) 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/cm 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.

The cerebral blood flow (CBF) alterations related to sound-induced opening of the blood-brain barrier (BBB) in adult mice are studied using laser speckle contrast imaging (LSCI) and wavelet analysis of vascular physiology. The results clearly show that the opening of the BBB is accompanied by the changes of venous but not microvessel circulation in the brain. The elevation of the BBB permeability is associated with the decrease of venous CBF and the increase of its complexity. These data suggest that the cerebral veins rather than microvessels are sensitive components of the CBF related to the opening BBB.

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.

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 out°ow and the loss of sensitivity of sagittal vein to vasoconstrictor e®ect of adrenaline. The incidence of ICH (24 h after stress) was accompanied by progression of early pathological changes in cerebral venous blood°ow (CVBF) and development of venous insu±ciency. Taking into consideration of this fact, we suggest that the suppression of CVBF related to the severity to the deleterious e®ect of stress on the brain hemodynamics in newborn rats. These facts allow us to conclude that the venous insu±ciency 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.

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.