In Vitro and In Vivo Study of the Short-Term Vasomotor Response during Epileptic Seizures

Epilepsy remains one of the most common brain disorders, and the different types of epilepsy encompass a wide variety of physiological manifestations. Clinical and preclinical findings indicate that cerebral blood flow is usually focally increased at seizure onset, shortly after the beginning of ictal events. Nevertheless, many questions remain about the relationship between vasomotor changes in the epileptic foci and the epileptic behavior of neurons and astrocytes. To study this relationship, we performed a series of in vitro and in vivo experiments using the 4-aminopyridine model of epileptic seizures. It was found that in vitro pathological synchronization of neurons and the depolarization of astrocytes is accompanied by rapid short-term vasoconstriction, while in vivo vasodilation during the seizure prevails. We suggest that vasomotor activity during epileptic seizures is a correlate of the complex, self-sustained response that includes neuronal and astrocytic oscillations, and that underlies the clinical presentation of epilepsy

Tissue Transparency In Vivo

In vivo tissue transparency in the visible light spectrum is beneficial for many research applications that use optical methods, whether it involves in vivo optical imaging of cells or their activity, or optical intervention to affect cells or their activity deep inside tissues, such as brain tissue. The classical view is that a tissue is transparent if it neither absorbs nor scatters light, and thus absorption and scattering are the key elements to be controlled to reach the necessary transparency. This review focuses on the latest genetic and chemical approaches for the decoloration of tissue pigments to reduce visible light absorption and the methods to reduce scattering in live tissues. We also discuss the possible molecules involved in transparency

Amyloid Beta Peptide Is Released during Thrombosis in the Skin

While it is known that amyloid beta (Aβ) deposits are found in different tissues of both Alzheimer’s disease (AD) patients and healthy individuals, there remain questions about the physiological role of these deposits, the origin of the Aβ peptide, and the mechanisms of its localization to the tissues. Using immunostaining with specific antibodies, as well as enzyme-linked immunosorbent assay, this study demonstrated Aβ40 peptide accumulation in the skin during local experimental photothrombosis in mice. Specifically, Aβ peptide accumulation was concentrated near the dermal blood vessels in thrombotic skin. It was also studied whether the released peptide affects microorganisms. Application of Aβ40 (4 µM) to the external membrane of yeast cells significantly increased membrane conductance with no visible effect on mouse host cells. The results suggest that Aβ release in the skin is related to skin injury and thrombosis, and occurs along with clotting whenever skin is damaged. These results support the proposition that Aβ release during thrombosis serves as part of a natural defense against infection

Platelet-generated amyloid beta peptides in Alzheimer’s disease and glaucoma

Amyloid beta (Aβ) peptides have been implicated in both Alzheimer’s disease (AD) and glaucoma and have been shown to be the key etiological factor in these dangerous health complications. On the other hand, it is well known that Aβ peptide can be generated from its precursor protein and massively released from the blood to nearby tissue upon the activation of platelets due to their involvement in innate immunity and inflammation processes. Here we review evidence about the development of AD and glaucoma neuronal damage showing their dependence on platelet count and activation. The correlation between the effect on platelet count and the effectiveness of anti-AD and anti-glaucoma therapies suggest that platelets may be an important player in these diseases

Spectral selectivity model for light transmission by the intermediate filaments in Muller cells

Presently we continue our studies of the quantum mechanism of light energy transmission in the form of excitons by axisymmetric nanostructures with electrically conductive walls. Using our theoretical model, we analyzed the light energy transmission by biopolymers forming optical channels within retinal Muller cells. There are specialized intermediate filaments (IF) 10-18 nm in diameter, built of electrically conductive polypeptides. Presently, we analyzed the spectral selectivity of these nanostructures. We found that their transmission spectrum depends on their diameter and wall thickness. We also considered the classical approach, comparing the results with those predicted by the quantum mechanism. We performed experimental measurements on model quantum waveguides, made of rectangular nanometer-thick chromium (Cr) tracks. The optical spectrum of such waveguides varied with their thickness. We compared the experimental absorption/transmission spectra with those predicted by our model, with good agreement between the two. We report that the observed spectra may be explained by the same mechanisms as operating in metal nanolayers. Both the models and the experiment show that Cr nanotracks have high light transmission efficiency in a narrow spectral range, with the spectral maximum dependent on the layer thickness. Therefore, a set of intermediate filaments with different geometries may provide light transmission over the entire visible spectrum with a very high (similar to 90%) efficiency. Thus, we believe that high contrast and visual resolution in daylight are provided by the quantum mechanism of energy transfer in the form of excitons, whereas the ultimate retinal sensitivity of the night vision is provided by the classical mechanism of photons transmitted by the Muller cell light-guides.PR NASA EPSCoR (NASA) [NNX13AB22A]NIH [G12 MD007583]Russian Science Foundation [16-14-10159]info:eu-repo/semantics/publishedVersio

Quantum mechanism of light energy propagation through an avian retina

Taking into account the ultrastructure of the Pied Flycatcher foveal retina reported earlier and the earlier reported properties of Muller cell (MC) intermediate filaments (IFs) isolated from vertebrate retina, we proposed a quantum mechanism (QM) of light energy transfer from the inner limiting membrane level to visual pigments in the photoreceptor cells. This mechanism involves electronic excitation energy transfer in a donor-acceptor system, with the IFs excited by photons acting as energy donors, and visual pigments in the photoreceptor cells acting as energy acceptors. It was shown earlier that IFs with diameter 10 nm and length 117 mu m isolated from vertebrate eye retina demonstrate properties of light energy guide, where exciton propagates along such IFs from MC endfeet area to photoreceptor cell area. The energy is mostly transferred via the contact exchange quantum mechanism. Our estimates demonstrate that energy transfer efficiencies in such systems may exceed 80-90%. Thus, the presently developed quantum mechanism of light energy transfer in the inverted retina complements the generally accepted classic optical mechanism and the mechanism whereby Muller cells transmit light like optical fibers. The proposed QM of light energy transfer in the inverted retina explains the high image contrast achieved in photopic conditions by an avian eye, being probably also active in other vertebrates.RSFRussian Science Foundation (RSF) [17-06-00404]PR NASA EPSCoR grant (NASA) [NNX15AK43A]NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [SC2GM111149]RSF grantRussian Science Foundation (RSF) [17-06-00404]info:eu-repo/semantics/publishedVersio

The Anti-Epileptic Effects of Carbenoxolone In Vitro and In Vivo

Gap junctions (GJs) are intercellular junctions that allow the direct transfer of ions and small molecules between neighboring cells, and GJs between astrocytes play an important role in the development of various pathologies of the brain, including regulation of the pathological neuronal synchronization underlying epileptic seizures. Recently, we found that a pathological change is observed in astrocytes during the ictal and interictal phases of 4-aminopyridin (4-AP)-elicited epileptic activity in vitro, which was correlated with neuronal synchronization and extracellular epileptic electrical activity. This finding raises the question: Does this signal depend on GJs between astrocytes? In this study we investigated the effect of the GJ blocker, carbenoxolone (CBX), on epileptic activity in vitro and in vivo. Based on the results obtained, we came to the conclusion that the astrocytic syncytium formed by GJ-associated astrocytes, which is responsible for the regulation of potassium, affects the formation of epileptic activity in astrocytes in vitro and epileptic seizure onset. This effect is probably an important, but not the only, mechanism by which CBX suppresses epileptic activity. It is likely that the mechanisms of selective inhibition of GJs between astrocytes will show important translational benefits in anti-epileptic therapies