In this pilot study, we analyzed effects of transcranial photobiomodulation (tPBM, 1267 nm, 32 J/cm 2 ) on clearance of beta-amyloid (Aβ) from the mouse brain. The immunohistochemical and confocal data clearly demonstrate the significant reduction of deposition of Aβ plaques in mice after tPBM vs. untreated animals. The behavior tests showed that tPBM improved the cognitive, memory and neurological status of mice with Alzheimer's disease (AD). Using of our original method based on optical coherence tomography (OCT) analysis of clearance of gold nanorods (GNRs) from the brain, we proposed possible mechanism underlying tPBM-stimulating effects on clearance of Aβ via the lymphatic system of the brain and the neck. These results open breakthrough strategies for a non-pharmacological therapy of Alzheimer's disease and clearly demonstrate that tPBM might be a promising therapeutic target for preventing or delaying Alzheimer's disease.

In this paper, measurements of the optical properties (diffuse reflectance, total and collimated transmittance) of brain tissues in healthy rats and rats with C6-glioma were performed in the spectral range from 350 to 1800 nm. Using these measurements, characteristic tissue optical parameters, such as absorption coefficient, scattering coefficient, reduced scattering coefficient, and scattering anisotropy factor were reconstructed. It was obtained that the 10-day development of glioma led to increase of absorption coefficient, which was associated with the water content elevation in the tumor. However, further development of the tumor (formation of the necrotic core) led to decrease in the water content. The dependence of the scattering properties on the different stages of model glioma development was more complex. Light penetration depth into the healthy and tumor brain was evaluated.

Alzheimer’s disease (AD) is an incurable pathology associated with progressive decline in memory and cognition. Phototherapy might be a new promising and alternative strategy for the effective treatment of AD, and has been actively discussed over two decades. However, the mechanisms of therapeutic photostimulation (PS) effects on subjects with AD remain poorly understood. The goal of this study was to determine the mechanisms of therapeutic PS effects in beta-amyloid (Aβ)-injected mice. The neurological severity score and the new object recognition tests demonstrate that PS 9 J/cm2 attenuates the memory and neurological deficit in mice with AD. The immunohistochemical assay revealed a decrease in the level of Aβ in the brain and an increase of Aβ in the deep cervical lymph nodes obtained from mice with AD after PS. Using the in vitro model of the blood-brain barrier (BBB), we show a PS-mediated decrease in transendothelial resistance and in the expression of tight junction proteins as well an increase in the BBB permeability to Aβ. These findings suggest that a PS-mediated BBB opening and the activation of the lymphatic clearance of Aβ from the brain might be a crucial mechanism underlying therapeutic effects of PS in mice with AD. These pioneering data open new strategies in the development of non-pharmacological methods for therapy of AD and contribute to a better understanding of the PS effects on the central nervous system.

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.

In this study, we analyzed the time-depended scenario of stress response cascade preceding and accompanying brain hemorrhages in newborn rats using an interdisciplinary approach based on: a morphological analysis of brain tissues, coherent-domain optical technologies for visualization of the cerebral blood flow, monitoring of the cerebral oxygenation and the deformability of red blood cells (RBCs). Using a model of stress-induced brain hemorrhages (sound stress, 120 dB, 370 Hz), we studied changes in neonatal brain 2, 4, 6, 8 h after stress (the pre-hemorrhage, latent period) and 24 h after stress (the post-hemorrhage period). We found that latent period of brain hemorrhages is accompanied by gradual pathological changes in systemic, metabolic, and cellular levels of stress. The incidence of brain hemorrhages is characterized by a progression of these changes and the irreversible cell death in the brain areas involved in higher mental functions. These processes are realized via a time-depended reduction of cerebral venous blood flow and oxygenation that was accompanied by an increase in RBCs deformability. The significant depletion of the molecular layer of the prefrontal cortex and the pyramidal neurons, which are crucial for associative learning and attention, is developed as a consequence of homeostasis imbalance. Thus, stress-induced processes preceding and accompanying brain hemorrhages in neonatal period contribute to serious injuries of the brain blood circulation, cerebral metabolic activity and structural elements of cognitive function. These results are an informative platform for further studies of mechanisms underlying stress-induced brain hemorrhages during the first days of life that will improve the future generation's health.

No abstract

Hemorrhagic insult is a major source of morbidity and mortality in both adults and newborn babies in the developed countries. The mechanisms underlying the non-traumatic rupture of cerebral vessels are not fully clear, but there is strong evidence that stress, which is associated with an increase in arterial blood pressure, plays a crucial role in the development of acute intracranial hemorrhage (ICH), and alterations in cerebral blood flow (CBF) may contribute to the pathogenesis of ICH. The problem is that there are no effective diagnostic methods that allow for a prognosis of risk to be made for the development of ICH. Therefore, quantitative assessment of CBF may significantly advance the understanding of the nature of ICH. The aim of this study was to determine the particularities of alterations in arterial and venous cerebral circulation in hypertensive rats at different stages of stress-related development of ICH using three-dimensional Doppler optical coherence tomography (DOCT).Experiments were performed in mongrel adult rats. To induce ICH, hypertensive rats underwent stress (effect of severe sound, 120 dB during 2 h). To induce the renal hypertension (two kidneys, one clip) the rats were clipped at the left renal artery with a silver clip. Seven weeks after clipping, the hypertensive rats were used in the experiment. The monitoring of CBF was performed in anesthetized rats with fixed heads using a commercially available swept source OCT system (OCS1300SS; Thorlabs) in the masked period of ICH (4 h after stress) and during ICH (24 h after stress).It could be shown that in stressed rats, compared with non-stressed animals, the latent stage of stress-induced ICH (4 h after stress-off) is characterized by an increase in diameter of the superior sagittal vein with decrease in speed of the blood flow in the venous network, whereas no changes in the CBF in the arterial tree were found in this period. These facts suggest that the masked period of ICH is accompanied by decreasing venous outflow and the development of venous insufficiency. The incidence of ICH, 24 h after stress, is associated with progression of pathological alterations in cerebral venous circulation. All hypertensive rats with ICH demonstrated a greater increase in the diameter of the superior sagittal vein than stressed rats at the latent stage of ICH (in 2.5-fold,In summary, using DOCT we have shown that the latent stage of stress-induced ICH is characterized by a decrease in venous outflow. The incidence of ICH is associated with the progression of pathological alterations in cerebral venous circulation that is accompanied by a decrease in blood flow in the arterial tree. The evaluation of cerebral venous insufficiency is an important diagnostic approach for the prognosis of the risk of developing cerebral hypotension and ICH.