Is blood-brain barrier a probable mediator of non-invasive brain stimulation effects on Alzheimer's disease?

Alzheimer's disease (AD) is a complex neurodegenerative disease with no existing treatment leading to full recovery. The blood-brain barrier (BBB) breakdown usually precedes the advent of first symptoms in AD and accompanies the progression of the disease. At the same time deliberate BBB opening may be beneficial for drug delivery in AD.

Distinct Effects of Beta-Amyloid, Its Isomerized and Phosphorylated Forms on the Redox Status and Mitochondrial Functioning of the Blood-Brain Barrier Endothelium.

The Alzheimer's disease (AD)-associated breakdown of the blood-brain barrier (BBB) promotes the accumulation of beta-amyloid peptide (Aβ) in the brain as the BBB cells provide Aβ transport from the brain parenchyma to the blood, and vice versa. The breakdown of the BBB during AD may be caused by the emergence of blood-borne Aβ pathogenic forms, such as structurally and chemically modified Aβ species; their effect on the BBB cells has not yet been studied. Here, we report that the effects of Aβ, Aβ, containing isomerized Asp7 residue (iso-Aβ) or phosphorylated Ser8 residue (p-Aβ) on the mitochondrial potential and respiration are closely related to the redox status changes in the mouse brain endothelial cells bEnd.

[Blood-Brain Barrier Transwell Modeling].

In vitro blood-brain barrier (BBB) modeling with the use of the brain endothelial cells grown on a transwell membrane is widely used to investigate BBB disorders and factors intended to ameliorate these pathologies. Endothelial cells, due to tight junction proteins, ensure selective permeability for a number of substances. The low integrity (i.

Na,K-ATPase Acts as a Beta-Amyloid Receptor Triggering Src Kinase Activation.

Beta-amyloid (Aβ) has a dual role, both as an important factor in the pathology of Alzheimer's disease and as a regulator in brain physiology. The inhibitory effect of Aβ oligomers on Na,K-ATPase contributes to neuronal dysfunction in Alzheimer's disease. Still, the physiological role of the monomeric form of Aβ interaction with Na,K-ATPase remains unclear.

Evaluation of Rat Brain Morphology Following the Induction of Acute Meningitis Treated with Ceftriaxone.

The soft and delicate tissue of the brain, which is the center of our coordination, is protected by its surrounding layers. The disruption of these layers results in complicated situations and serious health problems. The brain has three protective layers of bone or skull tissue, the blood tissue layer, and finally the meningeal layer.

Evaluation of Morphological and Histological Changes of Aggregated Lymph Nodes in the Small Intestine after Imofan Treatment in Immunosuppressed Rats.

Diffuse nodular lymphoid hyperplasia is a rare gastrointestinal disease that can be diagnosed by multiple nodules in the small intestine, large intestine, or both. Immunodeficiency and infections are the common situations that lead to the diffusion of nodular lymphoid hyperplasia. For instance, Giardia lamblia and are the major pathogens leading to this disorder.

Depth of the Steroid Core Location Determines the Mode of Na,K-ATPase Inhibition by Cardiotonic Steroids.

Cardiotonic steroids (CTSs) are specific inhibitors of Na,K-ATPase (NKA). They induce diverse physiological effects and were investigated as potential drugs in heart diseases, hypertension, neuroinflammation, antiviral and cancer therapy. Here, we compared the inhibition mode and binding of CTSs, such as ouabain, digoxin and marinobufagenin to NKA from pig and rat kidneys, containing CTSs-ensitive (α1) and -esistant (α1) α1-subunit, respectively.

Na /K imbalance contributes to gene expression in endothelial cells exposed to elevated NaCl.

High-salt consumption contributes to the development of hypertension and is considered an independent risk factor for vascular remodelling, cardiac hypertrophy and stroke incidence. Alterations in NO production, inflammation and endothelial cell stiffening are considered now as plausible mediators of cardiovascular dysfunction. We studied early responses of endothelial cells (HUVEC) caused by a moderate increase in extracellular sodium concentration.

Transcriptomic Changes in Endothelial Cells Triggered by Na,K-ATPase Inhibition: A Search for Upstream Na/K Sensitive Genes.

Stimulus-dependent elevation of intracellular Ca affects gene expression via well-documented calmodulin-mediated signaling pathways. Recently, we found that the addition of extra- and intracellular Ca chelators increased, rather than decreased, the number of genes expressed, and that this is affected by the elevation of [Na]/[K]-ratio. This assumes the existence of a novel Na/K-mediated Ca-independent mechanism of excitation-transcription coupling.

Ouabain-Induced Cell Death and Survival. Role of α1-Na,K-ATPase-Mediated Signaling and [Na]/[K]-Dependent Gene Expression.

Ouabain is of cardiotonic steroids (CTS) family that is plant-derived compounds and is known for many years as therapeutic and cytotoxic agents. They are specific inhibitors of Na,K-ATPase, the enzyme, which pumps Na and K across plasma membrane of animal cells. Treatment of cells by CTS affects various cellular functions connected with the maintenance of the transmembrane gradient of Na and K.

Na,K-ATPase as a target for endogenous cardiotonic steroids: What's the evidence?

With an exception of few reports, the plasma concentration of ouabain and marinobufagenin, mostly studied cardiotonic steroids (CTS) assessed by immunoassay techniques, is less than 1 nM. During the last 3 decades, the implication of these endogenous CTS in the pathogenesis of hypertension and other volume-expanded disorders is widely disputed. The threshold for inhibition by CTS of human and rodent α1-Na,K-ATPase is ∼1 and 1000 nM, respectively, that rules out the functioning of endogenous CTS (ECTS) as natriuretic hormones and regulators of cell adhesion, cell-to-cell communication, gene transcription and translation, which are mediated by dissipation of the transmembrane gradients of monovalent cations.

Search for Intracellular Sensors Involved in the Functioning of Monovalent Cations as Secondary Messengers.

Maintenance of non-equilibrium Na+ and K+ distribution between cytoplasm and extracellular medium suggests existence of sensors responding with conformational transitions to the changes of these monovalent cations' intracellular concentration. Molecular nature of monovalent cation sensors has been established in Na,K-ATPase, G-protein-coupled receptors, and heat shock proteins structural studies. Recently, it was found that changes in Na+ and K+ intracellular concentration are the key factors in the transcription and translation control, respectively.

[Primary uterine cervix melanoma].

The purpose of this paper is to present a rare clinical case of primary uterine cervix melanoma. Clinical data and histological specimens were a material for this investigation. The paper describes a case of primary uterine cervix melanoma in a 47-year-old patient who visited a gynecologist for contact bleeding from the genital tract.

Na⁺,K⁺-Dependent and -Independent Signaling Triggered by Cardiotonic Steroids: Facts and Artifacts.

Na⁺,K⁺-ATPase is the only known receptor of cardiotonic steroids (CTS) whose interaction with catalytic α-subunits leads to inhibition of this enzyme. As predicted, CTS affect numerous cellular functions related to the maintenance of the transmembrane gradient of monovalent cations, such as electrical membrane potential, cell volume, transepithelial movement of salt and osmotically-obliged water, symport of Na⁺ with inorganic phosphate, glucose, amino acids, nucleotides, etc. During the last two decades, it was shown that side-by-side with these canonical Na⁺/K⁺-dependent cellular responses, long-term exposure to CTS affects transcription, translation, tight junction, cell adhesion and exhibits tissue-specific impact on cell survival and death.

Time- and dose dependent actions of cardiotonic steroids on transcriptome and intracellular content of Na and K: a comparative analysis.

Recent studies demonstrated that in addition to Na,K-ATPase inhibition cardiotonic steroids (CTSs) affect diverse intracellular signaling pathways. This study examines the relative impact of [Na]/[K]-mediated and -independent signaling in transcriptomic changes triggered by the endogenous CTSs ouabain and marinobufagenin (MBG) in human umbilical vein endothelial cells (HUVEC). We noted that prolongation of incubation increased the apparent affinity for ouabain estimated by the loss of [K] and gain of [Na].

Effects of Ouabain on Proliferation of Human Endothelial Cells Correlate with Na+,K+-ATPase Activity and Intracellular Ratio of Na+ and K.

Side-by-side with inhibition of the Na+,K+-ATPase ouabain and other cardiotonic steroids (CTS) can affect cell functions by mechanisms other than regulation of the intracellular Na+ and K+ ratio ([Na+]i/[K+]i). Thus, we compared the dose- and time-dependences of the effect of ouabain on intracellular [Na+]i/[K+]i ratio, Na+,K+-ATPase activity, and proliferation of human umbilical vein endothelial cells (HUVEC). Treatment of the cells with 1-3 nM ouabain for 24-72 h decreased the [Na+]i/[K+]i ratio and increased cell proliferation by 20-50%.

Critical role of the α1-Na(+), K(+)-ATPase subunit in insensitivity of rodent cells to cytotoxic action of ouabain.

In rodents, ubiquitous α1-Na(+), K(+)-ATPase is inhibited by ouabain and other cardiotonic steroids (CTS) at ~10(3)-fold higher concentrations than those effective in other mammals. To examine the specific roles of the CTS-sensitive α1S- and CTS-resistant α1R-Na(+), K(+)-ATPase isoforms, we compared the effects of ouabain on intracellular Na(+) and K(+) content, cell survival, and mitogen-activated protein kinases (MAPK) in human and rat vascular smooth muscle cells (HASMC and RASMC), human and rat endothelial cells (HUVEC and RAEC), and human and rat brain astrocytes. 6-h exposure of HASMC and HUVEC to 3 μM ouabain dramatically increased the intracellular [Na(+)]/[K(+)] ratio to the same extend as in RASMC and RAEC treated with 3000 μM ouabain.

[Prognostic significance of lactate concentration and indicators of acid-base balance in air embolism of cerebral vessels].

Acid-base balance and lactate concentration in the arterial blood and spinal liquor have been studied in 32 patients after air embolism of the brain vessels developed during cardiopulmonary bypass surgery. It has been shown that an increase of lactate concentration in the spinal liquor over 3.5 mmol/l after air embolism of the brain vessels is indicative of severe hypoxic brain damage, in which the prospect of stable consciousness recovery is doubtful.

[Practical aspects of cardioplegia].

Concentrations of the ingredients have been analysed in a nonstandard cardioplegia solution (CS) and CS from St. Thomas Hospital at the outset before CS introduction into the coronary vessels of patients under cardioplegia. It has been shown that the use of nonstandard CS was accompanied by undesirable variability in ingredient concentration, which to some extent may be accounted for by the use of incompletely unfrozen CS.

[New parameters of the oxygen transport function of arterial blood].

New criteria of the arterial blood oxygen transport function suggested by O. Siggaard-Andersen et al. are reviewed.

[A new method of general anesthesia in pulmonary surgery using dalargin instead of narcotic analgesics].

Intraoperative and early postoperative parameters of the central hemodynamics, oxygen transport function and acid-base status of the blood, and blood lactic and pyruvic acid levels in patients under general anesthesia with dalargin were compared to those under traditional neuroleptic analgesia. The comparative evaluation allowed for a conclusion that general anaesthesia with dalargin provides for a reliable anesthesiological defence and exerts a lower deteriorating effect on the vessels of pulmonary circulation than traditional neuroleptic analgesia.

[Dalargin--a basic means of intraoperative protection of a patient during correction of an atrial septal defect under conditions of artificial circulation: a new method of anesthesia].

The paper presents results of application of the Soviet synthetic neuropeptide Dalargin as a major agent of anesthesiologic protection in the correction of a secondary atrial septal defect under general artificial circulation. From the findings obtained from examinations of central and peripheral hemodynamic parameters and blood oxygen transport function it was concluded that the anesthesiological protection was adequate at all the stages of an operation. The authors also give data on the optimization of the afterload of the right ventricle and preload of the left ventricle under anesthesia in which dalargin was used by directly affecting the elasticity of pulmonary vessels.