Arkady Abdurashitov

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.

The Stress and Vascular Catastrophes in Newborn Rats: Mechanisms Preceding and Accompanying the Brain Hemorrhages

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 generations health.

Application of optical coherence tomography for in vivo monitoring of the meningeal lymphatic vessels during opening of blood–brain barrier: mechanisms of brain clearing

Abstract. The meningeal lymphatic vessels were discovered 2 years ago as the drainage system involved in the mechanisms underlying the clearance of waste products from the brain. The blood–brain barrier (BBB) is a gatekeeper that strongly controls the movement of different molecules from the blood into the brain. We know the scenarios during the opening of the BBB, but there is extremely limited information on how the brain clears the substances that cross the BBB. Here, using the model of sound-induced opening of the BBB, we clearly show how the brain clears dextran after it crosses the BBB via the meningeal lymphatic vessels. We first demonstrate successful application of optical coherence tomography (OCT) for imaging of the lymphatic vessels in the meninges after opening of the BBB, which might be a new useful strategy for noninvasive analysis of lymphatic drainage in daily clinical practice. Also, we give information about the depth and size of the meningeal lymphatic vessels in mice. These new fundamental data with the applied focus on the OCT shed light on the mechanisms of brain clearance and the role of lymphatic drainage in these processes that could serve as an informative platform for a development of therapy and diagnostics of diseases associated with injuries of the BBB such as stroke, brain trauma, glioma, depression, or Alzheimer disease.

Silent Vascular Catastrophes in the Brain in Term Newborns: Strategies for Optical Imaging

In this review, we describe the phenomenon of intra-cranial hemorrhage (ICH), which occurs spontaneously within the first 2-3 days of life in full-term newborns without any clinical symptoms, but with long-term neurological outcomes in many cases. We give the estimated frequency and possible mechanisms responsible for silent ICH with main focus on the cerebral blood flow (CBF) and oxygenation measurements using noninvasive optical methods. We overview the current multi-modal technologies that are widely used in clinics and experiments for the study of ICH during the first days of life: magnetic resonance imaging, ultrasonography, cerebral oximetry based on near infrared spectroscopy, as well as laser speckle imaging and diffuse correlation spectroscopy as a priority technology for experimental study of cerebral hemodynamics. We discuss the advantages and disadvantages of these methods. We identify key trends in experimental works and show areas for future research of ICH in term newborns. Future studies will help to improve our ability to optimize prognosis, diagnosis, and treatment of asymptomatic neonates with silent ICH.

Changes in the cerebral blood flow in newborn rats assessed by LSCI and DOCT before and after the hemorrhagic stroke

The incidence of perinatal hemorrhagic stroke (HS) is very similar to that in the elderly and produces a significant morbidity and long-term neurologic and cognitive deficits. There is strong evidence that cerebral blood flow (CBF) abnormalities make considerable contribution to HS development. However, the mechanisms responsible for pathological changes in CBF in infants with HS are not established. Therefore, quantitative assessment of CBF may significantly advance the understanding of the nature of neonatal stroke. The aim of this investigation was to determine the particularities of alterations in macro- microcirculation in the brain of newborn rats in the different stages of stress-related development of HS using three-dimensional Doppler optical coherence tomography (DOCT) and laser speckle contrast imaging (LSCI).Our results show that cerebral veins are more sensitive to harmful effect of stress compared with microcirculatory vessels. Stress-induced progressive dilation of cerebral veins with the fall of blood flow velocity precedes HS while pathological changes in microcirculatory vessels are accompanied by development of HS. The further detailed study of cerebral venous and microcirculatory circulation would be a significant advance in development of prognostic criteria for a HS risk during the first days after birthday.

Characterizing scaling properties of complex signals with missed data segments using the multifractal analysis

The scaling properties of complex processes may be highly influenced by the presence of various artifacts in experimental recordings. Their removal produces changes in the singularity spectra and the Hölder exponents as compared with the original artifacts-free data, and these changes are significantly different for positively correlated and anti-correlated signals. While signals with power-law correlations are nearly insensitive to the loss of significant parts of data, the removal of fragments of anti-correlated signals is more crucial for further data analysis. In this work, we study the ability of characterizing scaling features of chaotic and stochastic processes with distinct correlation properties using a wavelet-based multifractal analysis, and discuss differences between the effect of missed data for synchronous and asynchronous oscillatory regimes. We show that even an extreme data loss allows characterizing physiological processes such as the cerebral blood flow dynamics.

Multifractal spectrum of physiological signals: a mechanism-related approach

In this paper we discuss an approach for mechanism-related analysis of physiological signals performed with the wavelet-based multifractal formalism. This approach assumes estimation of the singularity spectrum for the band-pass filtered processes at different physiological conditions in order to provide explanation of the occurred changes in the Hölder exponents and the multi-fractality degree. We illustrate the considered approach using two examples, namely, the dynamics of the cerebral blood flow (CBF) and the electrical activity of the brain.

Optical coherent tomography and fluorescent microscopy for the study of meningeal lymphatic systems

The development of novel technologies for the imaging of meningeal lymphatic vessels is one of the amazing trends of biophotonics thanks to discovery of brain lymphatics over several years ago. However, there is the limited technologies exist for the study of lymphatics in vivo because lymphatic vessels are transparent with a low speed flow of lymph. Here we demonstrate the successful application of fluorescent microscopy for the imaging of lymphatic system in the mouse brain in vivo.

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.

The lymphatic mechanisms of brain cleaning: application of optical coherence tomography and fluorescence microscopy

Here we studied the role of cerebral lymphatic system in the brain clearing using intraparenchymal injection of Evans Blue and gold nanorods assessed by optical coherent tomography and fluorescence microscopy. Our data clearly show that the cerebral lymphatic system plays an important role in the brain cleaning via meningeal lymphatic vessels but not cerebral veins. Meningeal lymphatic vessels transport fluid from the brain into the deep cervical node, which is the first anatomical “station” for lymph outflow from the brain. The lymphatic processes underlying brain clearing are more slowly vs. peripheral lymphatics. These results shed light on the lymphatic mechanisms responsible for brain clearing as well as interaction between the intra- and extracranial lymphatic compartment.