Characterization of Anesthesia in Rats from EEG in Terms of Long-Range Correlations.

Long-range correlations are often used as diagnostic markers in physiological research. Due to the limitations of conventional techniques, their characterizations are typically carried out with alternative approaches, such as the detrended fluctuation analysis (DFA). In our previous works, we found EEG-related markers of the blood-brain barrier (BBB), which limits the penetration of major drugs into the brain. However, anesthetics can penetrate the BBB, affecting its function in a dose-related manner. Here, we study two types of anesthesia widely used in experiments on animals, including zoletil/xylazine and isoflurane in optimal doses not associated with changes in the BBB. Based on DFA, we reveal informative characteristics of the electrical activity of the brain during such doses that are important for controlling the depth of anesthesia in long-term experiments using magnetic resonance imaging, multiphoton microscopy, etc., which are crucial for the interpretation of experimental results. These findings provide an important informative platform for the enhancement and refinement of surgery, since the EEG-based DFA analysis of BBB can easily be used during surgery as a tool for characterizing normal BBB functions under anesthesia.

Extended Detrended Fluctuation Analysis of Coarse-Grained Time Series.

A coarse-graining procedure, which involves averaging time series in non-overlapping windows followed by processing of the obtained multiple data sets, is the initial step in the multiscale entropy computation method. In this paper, we discuss how this procedure can be applied with other methods of time series analysis. Based on extended detrended fluctuation analysis (EDFA), we compare signal processing results for data sets with and without coarse-graining. Using the simulated data provided by the interacting nephrons model, we show how this procedure increases, up to 48%, the distinctions between local scaling exponents quantifying synchronous and asynchronous chaotic oscillations. Based on the experimental data of electrocorticograms (ECoG) of mice, an improvement in differences in local scaling exponents up to 41% and Student's t-values up to 34% was revealed.

Anodal Transcranial Direct Current Stimulation Improves Impaired Cerebrovascular Reactivity in Traumatized Mouse Brain.

Cerebrovascular reactivity (CVR) is a compensatory mechanism where blood vessels dilate in response to a vasodilatory stimulus, and is a biomarker of vascular reserve and microvascular health. Impaired CVR indicates microvascular hemodynamic dysfunction, which is implicated in traumatic brain injury (TBI) and associated with long-term neurological deficiency. Recently we have shown that anodal transcranial direct current stimulation (tDCS) caused prolonged dilatation of cerebral arterioles that increased brain microvascular flow and tissue oxygenation in traumatized mouse brain and was associated with neurologic improvement. Here we evaluate the effects of tDCS on impaired CVR and microvascular cerebral blood flow (mCBF) regulation after TBI. TBI was induced in mice by controlled cortical impact (CCI). Cortical microvascular tone, mCBF, and tissue oxygen supply (by nicotinamide adenine dinucleotide, NADH) were measured by two-photon laser scanning microscopy before and after anodal tDCS (0.1 mA/15 min). CVR and mCBF regulation were evaluated by measuring changes in arteriolar diameters and NADH during hypercapnia test before and after tDCS. Transient hypercapnia was induced by 60-s increase of CO2 concentration in the inhalation mixture to 10%. As previously, anodal tDCS dilated arterioles which increased arteriolar blood flow volume that led to an increase in capillary flow velocity and the number of functioning capillaries, thereby improving tissue oxygenation in both traumatized and sham animals. In sham mice, transient hypercapnia caused transient dilatation of cerebral arterioles with constant NADH, reflecting intact CVR and mCBF regulation. In TBI animals, arteriolar dilatation response to hypercapnia was diminished while the NADH level increased (tissue oxygen supply decreased), reflecting impaired CVR and mCBF regulation. Anodal tDCS enhanced reactivity in parenchymal arterioles in both groups (especially in TBI mice) and restored CVR thereby prevented the reduction in tissue oxygen supply during hypercapnia. CVR has been shown to be related to nitric oxide elevation due to nitric oxide synthases activation, which can be sensitive to the electrical field induced by tDCS.

Simulating Dynamics of Circulation in the Awake State and Different Stages of Sleep Using Non-autonomous Mathematical Model With Time Delay.

We propose a mathematical model of the human cardiovascular system. The model allows one to simulate the main heart rate, its variability under the influence of the autonomic nervous system, breathing process, and oscillations of blood pressure. For the first time, the model takes into account the activity of the cerebral cortex structures that modulate the autonomic control loops of blood circulation in the awake state and in various stages of sleep. The adequacy of the model is demonstrated by comparing its time series with experimental records of healthy subjects in the SIESTA database. The proposed model can become a useful tool for studying the characteristics of the cardiovascular system dynamics during sleep.

Optical properties of brain tissues at the different stages of glioma development in rats: pilot study.

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.

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.

Gliotransmitters and cytokines in the control of blood-brain barrier permeability.

The contribution of astrocytes and microglia to the regulation of neuroplasticity or neurovascular unit (NVU) is based on the coordinated secretion of gliotransmitters and cytokines and the release and uptake of metabolites. Blood-brain barrier (BBB) integrity and angiogenesis are influenced by perivascular cells contacting with the abluminal side of brain microvessel endothelial cells (pericytes, astrocytes) or by immune cells existing (microglia) or invading the NVU (macrophages) under pathologic conditions. The release of gliotransmitters or cytokines by activated astroglial and microglial cells is provided by distinct mechanisms, affects intercellular communication, and results in the establishment of microenvironment controlling BBB permeability and neuroinflammation. Glial glutamate transporters and connexin and pannexin hemichannels working in the tight functional coupling with the purinergic system serve as promising molecular targets for manipulating the intercellular communications that control BBB permeability in brain pathologies associated with excessive angiogenesis, cerebrovascular remodeling, and BBB-mediated neuroinflammation. Substantial progress in deciphering the molecular mechanisms underlying the (patho)physiology of perivascular glia provides promising approaches to novel clinically relevant therapies for brain disorders. The present review summarizes the current understandings on the secretory machinery expressed in glial cells (glutamate transporters, connexin and pannexin hemichannels, exocytosis mechanisms, membrane-derived microvesicles, and inflammasomes) and the role of secreted gliotransmitters and cytokines in the regulation of NVU and BBB permeability in (patho)physiologic conditions.

Off-axis holographic laser speckle contrast imaging of blood vessels in tissues.

Laser speckle contrast imaging (LSCI) has become one of the most common tools for functional imaging in tissues. Incomplete theoretical description and sophisticated interpretation of measurement results are completely sidelined by a low-cost and simple hardware, fastness, consistent results, and repeatability. In addition to the relatively low measuring volume with around 700 ?? ? m of the probing depth for the visible spectral range of illumination, there is no depth selectivity in conventional LSCI configuration; furthermore, in a case of high NA objective, the actual penetration depth of light in tissues is greater than depth of field (DOF) of an imaging system. Thus, the information about these out-of-focus regions persists in the recorded frames but cannot be retrieved due to intensity-based registration method. We propose a simple modification of LSCI system based on the off-axis holography to introduce after-registration refocusing ability to overcome both depth-selectivity and DOF problems as well as to get the potential possibility of producing a cross-section view of the specimen.