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Distribution of extracellular fluid over the intra- and extravascular space in hypertensive patients.

The time course of hemodynamic responses to long-standing sodium overload was studied in humans. The study involved six patients who became hypertensive on exposure to excessive mineralocorticoid activity. Arterial pressure, cardiac output, and body fluid volumes were measured with noninvasive methods at weekly intervals for at least 6 weeks and at longer intervals for periods up to 2 years. Extracellular fluid volume was expanded by approximately 20%, and arterial blood pressure rose by 20-40%. Initially, cardiac output was the dominant factor for the pressure rise. But in a later stage the p

Aβ Deposition in Extracellular Space Disrupts Glial-Neuron Communication and Triggers Alzheimer's Disease.

Disruptions in glial-neuron communication are linked to brain diseases; however, the exact mechanisms are not yet fully understood. This rev … er's Disease (AD). In AD, astrocytes use APOE to increase amyloid-beta (Aβ) deposition in the brain extracellular space (ECS) and neuron death, while microglia overactivation causes Tau overexpression and oligodendrocyte demyelination, leading to communication issues. Toxic proteins, Aβ and Tau, block brain ECS and hinder the drainage of interstitial fluid (ISF) caus …

Dead-Space Microdomains as Explicit Barriers to Extracellular Drug Transport in Alzheimer's Disease.

OBJECTIVE: The impact of dead-space (DS) microdomains on cerebral drug penetration has been demonstrated experimentally; yet computational models typically capture their effects indirectly through effective tortuosity parameters. Here, we develop an anatomically grounded framework that systematically evaluates pharmaceutical diffusion within the central nervous system (CNS). METHODS: A finite element (FE) model was developed with DS explicitly represented as impermeable obstructions in the extracellular space (ECS) - consistent with structural remodeling observed in Alzheimer's disease (AD). …

Glucose uptake is essential for Brucella abortus growth in the extracellular space of the murine placenta.

Brucella abortus infects the placenta of its natural bovine host, which results in abortion and transmission of infection to other cattle and to humans. While the metabolism of B. abortus during chronic infection of the mononuclear phagocyte system has been studied, the nutrients fueling growth of B. abortus in the placenta are unknown. We found that in mice, glucose is an important carbon source for B. abortus in the placenta. A gluP mutant lacking a major facilitator superfamily protein required for glucose uptake had diminished growth in the placenta of pregnant mice and caused reduced infl

Characterization of the Ionic Profile of the Extracellular Space of the Injured and Ischemic Brain: A Microdialysis Study.

Traumatic brain injury (TBI) and ischemic stroke cause a variable disruption of ionic homeostasis and massive ionic fluxes with subsequent osmotic water movement across the cells that causes edema, brain swelling, and deformation of the damaged tissue. Although cerebral microdialysis (CMD) has been used to study the brain neurochemistry, the ionic profiles of brain interstitial space fluid have rarely been reported in humans. We studied the ionic profile in injured areas of the brain by using CMD. As a control group, we included seven patients who had undergone surgical treatment of posterior

Wild-type huntingtin participates in protein trafficking between the Golgi and the extracellular space.

Huntington disease (HD) is an autosomal dominant neurodegenerative disease caused by an expanded CAG trinucleotide repeat in the first exon … gtin null neurons exhibit a significant reduction in transcripts encoding proteins destined for the extracellular space, many of which are components of the extracellular matrix or involved in cellular adhesion, receptor binding and hormone activity. Together, these findings support a role for huntingtin in the intracellular trafficking of proteins required for the c …

pH, K+, and PO2 of the extracellular space during ischaemia of primate cerebral cortex.

pH and K+ from the extracellular space, PO2, and CBF have been measured in the same region during progressive ischaemia of primate cerebral cortex. As blood flow was reduced, the other changes had the following sequence. PO2 fell rapidly to 30% of control levels at regional CBF (rCBF) of 30 ml 100 g-1 min-1. As CBF was further reduced, PO2 continued to fall. pH remained stable until around 20 ml 100 g-1 min-1, below which pH fell rapidly, with an exponential increase in H+ concentration. K+ showed the well-known relationship to CBF, remaining normal until around 10 ml 100 g-1 min-1, below whic…

Mitovesicles secreted into the extracellular space of brains with mitochondrial dysfunction impair synaptic plasticity.

BACKGROUND: Hypometabolism tied to mitochondrial dysfunction occurs in the aging brain and in neurodegenerative disorders, including in Alzheimer's disease, in Down syndrome, and in mouse models of these conditions. We have previously shown that mitovesicles, small extracellular vesicles (EVs) of mitochondrial origin, are altered in content and abundance in multiple brain conditions characterized by mitochondrial dysfunction. However, given their recent discovery, it is yet to be explored what mitovesicles regulate and modify, both under physiological conditions and in the diseased brain. In t

[Imaging and quantitative measurement of brain extracellular space using MRI Gd-DTPA tracer method].

OBJECTIVE: To observe the diffusion of Gd-DTPA in brain extracellular space (ECS) by magnetic resonance imaging(MRI) and investigate the feasibility of ECS measurement by using MRI tracer method in vivo. METHODS: 2 microL Gd-DTPA was introduced into ECS by caudate nucleus according to stereotaxic atlas in 8 Sprague Dawley(SD) rats (male, 280-320 g). The MRI scans were performed at 1 h, 3 h, 6 h, 9 h and 12 h respectively after administration. MRI appearances of Gd-DTPA diffusion and distribution was observed and compared. The MRI signal enhancement was measured at each time point. The neuroet…

Quantitative analysis of molecular transport in the extracellular space using physics-informed neural network.

The brain extracellular space (ECS), an irregular, extremely tortuous nanoscale space located between cells or between cells and blood vessels, is crucial for nerve cell survival. It plays a pivotal role in high-level brain functions such as memory, emotion, and sensation. However, the specific form of molecular transport within the ECS remain elusive. To address this challenge, this paper proposes a novel approach to quantitatively analyze the molecular transport within the ECS by solving an inverse problem derived from the advection-diffusion equation (ADE) using a physics-informed neural ne…

Эффективная основа для изучения передачи сигналов из-за однородного внеклеточного пространства в нейронах.

Исследования скорости проведения нервы необходимы для понимания неврологических расстройств, таких как ALS, синдром Гильен-Барре, болезнь Шаркот-Мари-Зуб, синдром запястьевого туннельного туннеля, нервно-паралитические расстройства и множественный склероз, которые характеризуются замедлением сигнала. Различные ионы в внеклеточном пространстве (ЭКС) и волокна нерва регулируют распространение сигнала, что делает чрезвычайно важным анализ воздействия ECS на передачу сигнала. В этом исследовании рассматривается вопрос о том, как неоднородное внеклеточное пространство влияет на скорость проводимого

Совпадение в аннотации оригинала
Nerve conduction velocity studies are essential to understanding neurological disorders like ALS, Guillain-Barré syndrome, Charcot-Marie-Tooth disease, carpal tunnel syndrome, sciatic nerve disorders, and multiple sclerosis, which are marked by slowed signal conduction. Various ions in the extracellular space (ECS) and the nerve fiber regulate signal propaga…

HAP40 functions as a proteostasis regulator by controlling huntingtin interactions and its release into the extracellular space.

Huntingtin-associated protein 40 (HAP40) forms a stable protein complex with huntingtin (HTT). Its cellular function and how HAP40 loss influences mutant HTT (mHTT) abundance and pathobiology are currently unclear. Here, using diverse cellular models and omics methods, we demonstrate that HAP40 is an obligate interaction partner of HTT and through its binding controls HTT interactions and the abundance of HTT-associated proteins, indicating that it functions as a HTT interaction regulatory unit. Also, loss of HAP40 in mHTT-expressing striatal cells impairs autophagic protein degradation and tr

Release of FUS into the extracellular space is regulated by its amino-terminal prion-like domain.

Fused in sarcoma (FUS) is a causative factor of amyotrophic lateral sclerosis (ALS) and is believed to propagate pathologically by transmission from cell to cell. However, the mechanism underlying FUS release from cells, which is a critical step for the propagation system, remains poorly understood. This study conducted an analysis of the release of human and mouse FUS from neurons, revealing that human FUS is significantly released into the media compared to its mouse counterpart. Further study using chimeric FUS proteins identified the amino-terminal region of human FUS as essential for its

Simultaneous Mapping of the Nanoscale Organization and Redox State of Extracellular Space in Living Brain Tissue.

The spatial organization characteristics and redox status of the extracellular space (ECS) are crucial in the development of brain diseases. However, it remains a challenge to simultaneously capture dynamic changes in microstructural features and redox states at the submicron level within the ECS. Here, we developed a reversible glutathione (GSH)-responsive nanoprobe (RGN) for mapping the spatial organization features and redox status of the ECS in brain tissues with nanoscale resolution. The RGN is composed of polymer nanoparticles modified with GSH-responsive molecules and amino-functionaliz…

Local Echo-Free Space in a Limb with Lymphedema Represents Extracellular Fluid in the Entire Limb.

BACKGROUND: We previously reported that local subcutaneous echo-free space (SEFS) in the leg was stirringly correlated with extracellular fluid (ECF) status in the same part of the leg when assessed using bioelectrical impedance analysis (BIA). In this study, we examined whether local SEFS represents the ECF status in the entire limb. METHODS AND RESULTS: In 51 legs and 40 arms with lymphedema (LE), subcutaneous tissue ultrasonography was performed to determine SEFS severity (range, 0-2). BIA was also performed to calculate the L-Dex® score (LDS), which is a BIA-derived parameter to represent

The source of net ultrafiltration during hemodialysis is mostly the extracellular space regardless of hydration status.

Fluid shifts are common in patients undergoing chronic hemodialysis (HD) during the intradialytic periods, as several liters of fluid are re … id shifts were observed according to hydration status. The source of net UF during HD is mostly the extracellular space regardless of hydration status. Thus, IDH may be related to differences in the interstitial fluid shift to the vascular space.

Efficacy of Citicoline Delivered via Brain Extracellular Space against Experimental Acute Ischemic Stroke in Rats.

Objective: Citicoline can be used to reduce acute ischemic stroke injury via venous infusion, however, its protective effects in the brain extracellular space remain largely unknown. Herein, we investigated the brain protective effects of citicoline administered via the brain extracellular space and sought precise effective dosage range that can protect against ischemic injury after experimental ischemic stroke in rats. Methods: Fifty-six Sprague-Dawley rats were randomly divided into control, intraperitoneal (IP), caudate-putamen (CPu)-25, CPu-40, CPu-50, CPu-60 and CPu-75 groups based on the…

Mapping Extracellular Space Features of Viral Encephalitis to Evaluate the Proficiency of Anti-Viral Drugs.

The extracellular space (ECS) is an important barrier against viral attack on brain cells, and dynamic changes in ECS microstructure characteristics are closely related to the progression of viral encephalitis in the brain and the efficacy of antiviral drugs. However, mapping the precise morphological and rheological features of the ECS in viral encephalitis is still challenging so far. Here, a robust approach is developed using single-particle diffusional fingerprinting of quantum dots combined with machine learning to map ECS features in the brain and predict the efficacy of antiviral enceph…