Membrane structure in mammalian astrocytes: a review of freeze-fracture studies on adult, developing, reactive and cultured astrocytes

1981 ◽  
Vol 95 (1) ◽  
pp. 35-48
Author(s):  
D. M. Landis ◽  
T. S. Reese
Keyword(s):  
Cerebrospinal Fluid ◽  
Membrane Structure ◽  
Plasma Membranes ◽  
Freeze Fracture ◽  
Brain Parenchyma ◽  
Specific Pattern ◽  
Cultured Astrocytes ◽  
Fluid Compartments ◽  
Polygonal Particle ◽  
The Brain

The application of freeze-fracture techniques to studies of brain structure has led to the recognition of two unsuspected specializations of membrane structure, each distributed in a specific pattern across the surface of astrocytes. ‘Assemblies’ (aggregates of uniform, small particles packed in orthogonal array into rectangular or square aggregates) are found to characterize astrocytic plasma membranes apposed to blood vessels or to the cerebrospinal fluid at the surface of the brain. These particle aggregates are much less densely packed in astrocytic processes in brain parenchyma. Assemblies are not fixation artifacts, have been shown to extend to the true outer surface of the membrane, are remarkably labile in the setting of anoxia, and are at least in part protein. The function of assemblies is unknown, but their positioning suggests that they may have a role in the transport of some material into or out of the blood and cerebrospinal fluid compartments. A second specialization of intramembrane particle distribution, the polygonal particle junction, links astrocytic processes at the surface of the brain, and also links proximal, large caliber astrocytic processes in brain parenchyma. The function of this membrane specialization also is unknown, but it may subserve a mechanical role.

scholarly journals The Potential Roles of Blood–Brain Barrier and Blood–Cerebrospinal Fluid Barrier in Maintaining Brain Manganese Homeostasis

Nutrients ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1833
Author(s):  
Shannon Morgan McCabe ◽  
Ningning Zhao
Keyword(s):  
Cerebrospinal Fluid ◽  
Blood Brain Barrier ◽  
Blood Circulation ◽  
Critical Role ◽  
Systemic Circulation ◽  
Brain Parenchyma ◽  
Brain Barrier ◽  
Blood Brain ◽  
The Brain

Manganese (Mn) is a trace nutrient necessary for life but becomes neurotoxic at high concentrations in the brain. The brain is a “privileged” organ that is separated from systemic blood circulation mainly by two barriers. Endothelial cells within the brain form tight junctions and act as the blood–brain barrier (BBB), which physically separates circulating blood from the brain parenchyma. Between the blood and the cerebrospinal fluid (CSF) is the choroid plexus (CP), which is a tissue that acts as the blood–CSF barrier (BCB). Pharmaceuticals, proteins, and metals in the systemic circulation are unable to reach the brain and spinal cord unless transported through either of the two brain barriers. The BBB and the BCB consist of tightly connected cells that fulfill the critical role of neuroprotection and control the exchange of materials between the brain environment and blood circulation. Many recent publications provide insights into Mn transport in vivo or in cell models. In this review, we will focus on the current research regarding Mn metabolism in the brain and discuss the potential roles of the BBB and BCB in maintaining brain Mn homeostasis.

scholarly journals Mechanism of Coup and Contrecoup Injuries Induced by a Knock-Out Punch

2020 ◽  
Vol 25 (2) ◽  
pp. 22 ◽  
Author(s):  
Milan Toma ◽  
Rosalyn Chan-Akeley ◽  
Christopher Lipari ◽  
Sheng-Han Kuo
Keyword(s):  
Cerebrospinal Fluid ◽  
Interaction Model ◽  
Brain Parenchyma ◽  
Primary Objective ◽  
Element Analysis ◽  
Knock Out ◽  
Particle Hydrodynamics ◽  
Smoothed Particle ◽  
The Impact ◽  
The Brain

Primary Objective: The interaction of cerebrospinal fluid with the brain parenchyma in an impact scenario is studied. Research Design: A computational fluid-structure interaction model is used to simulate the interaction of cerebrospinal fluid with a comprehensive brain model. Methods and Procedures: The method of smoothed particle hydrodynamics is used to simulate the fluid flow, induced by the impact, simultaneously with finite element analysis to solve the large deformations in the brain model. Main Outcomes and Results: Mechanism of injury resulting in concussion is demonstrated. The locations with the highest stress values on the brain parenchyma are shown. Conclusions: Our simulations found that the damage to the brain resulting from the contrecoup injury is more severe than that resulting from the coup injury. Additionally, we show that the contrecoup injury does not always appear on the side opposite from where impact occurs.

scholarly journals Astrocyte membrane structure: changes after circulatory arrest.

1981 ◽  
Vol 88 (3) ◽  
pp. 660-663 ◽  
Author(s):  
D M Landis ◽  
T S Reese
Keyword(s):  
Membrane Structure ◽  
Circulatory Arrest ◽  
Freeze Fracture ◽  
Rapid Freezing ◽  
Normal Numbers ◽  
Membrane Specialization ◽  
Structure Changes ◽  
Glial Membrane ◽  
The Brain

Membranes of the astrocytic processes investing small blood vessels and the surface of the brain contain numerous arrays of orthogonally packed particles as revealed by the freeze-fracture technique. The structure of these particle arrays, which we have termed "assemblies," is the same whether tissue is prepared for freeze-fracture by conventional fixation or by quick excision and rapid freezing. However, assemblies are progressively replaced by amorphous clumps and then disappear as the interval between decapitation and rapid freezing increases. Nearly normal numbers of assemblies may be maintained in cerebellar slices in vitro, but there too they disappear at low PO2 or in the presence of dinitrophenol. No other neuronal or glial membrane specialization exhibits a comparable lability.

scholarly journals Nanoparticle brain delivery: a guide to verification methods

Nanomedicine ◽  
2020 ◽  
Vol 15 (4) ◽  
pp. 409-432 ◽  
Author(s):  
Robert A Yokel
Keyword(s):  
Cerebrospinal Fluid ◽  
Extracellular Space ◽  
Brain Parenchyma ◽  
Brain Delivery ◽  
Peripheral Organ ◽  
Blood Brain ◽  
Verification Methods ◽  
Brain Parenchymal ◽  
And Function ◽  
The Brain

Many reports conclude nanoparticle (NP) brain entry based on bulk brain analysis. Bulk brain includes blood, cerebrospinal fluid and blood vessels within the brain contributing to the blood–brain and blood–cerebrospinal fluid barriers. Considering the brain as neurons, glia and their extracellular space (brain parenchyma), most studies did not show brain parenchymal NP entry. Blood–brain and blood–cerebrospinal fluid barriers anatomy and function are reviewed. Methods demonstrating brain parenchymal NP entry are presented. Results demonstrating bulk brain versus brain parenchymal entry are classified. Studies are reviewed, critiqued and classified to illustrate results demonstrating bulk brain versus parenchymal entry. Brain, blood and peripheral organ NP timecourses are compared and related to brain parenchymal entry evidence suggesting brain NP timecourse informs about brain parenchymal entry.

The betaine-GABA transporter (BGT1, slc6a12) is predominantly expressed in the liver and at lower levels in the kidneys and at the brain surface

2012 ◽  
Vol 302 (3) ◽  
pp. F316-F328 ◽  
Author(s):  
Y. Zhou ◽  
S. Holmseth ◽  
R. Hua ◽  
A. C. Lehre ◽  
A. M. Olofsson ◽  
...  
Keyword(s):  
Plasma Membranes ◽  
Renal Medulla ◽  
Brain Parenchyma ◽  
Ependymal Cells ◽  
Main Role ◽  
Mrna Levels ◽  
Physiological Importance ◽  
Brain Surface ◽  
Negative Controls ◽  
The Brain

The Na+- and Cl−-dependent GABA-betaine transporter (BGT1) has received attention mostly as a protector against osmolarity changes in the kidney and as a potential controller of the neurotransmitter GABA in the brain. Nevertheless, the cellular distribution of BGT1, and its physiological importance, is not fully understood. Here we have quantified mRNA levels using TaqMan real-time PCR, produced a number of BGT1 antibodies, and used these to study BGT1 distribution in mice. BGT1 (protein and mRNA) is predominantly expressed in the liver (sinusoidal hepatocyte plasma membranes) and not in the endothelium. BGT1 is also present in the renal medulla, where it localizes to the basolateral membranes of collecting ducts (particularly at the papilla tip) and the thick ascending limbs of Henle. There is some BGT1 in the leptomeninges, but brain parenchyma, brain blood vessels, ependymal cells, the renal cortex, and the intestine are virtually BGT1 deficient in 1- to 3-mo-old mice. Labeling specificity was assured by processing tissue from BGT1-deficient littermates in parallel as negative controls. Addition of 2.5% sodium chloride to the drinking water for 48 h induced a two- to threefold upregulation of BGT1, tonicity-responsive enhancer binding protein, and sodium- myo-inositol cotransporter 1 (slc5a3) in the renal medulla, but not in the brain and barely in the liver. BGT1-deficient and wild-type mice appeared to tolerate the salt treatment equally well, possibly because betaine is one of several osmolytes. In conclusion, this study suggests that BGT1 plays its main role in the liver, thereby complementing other betaine-transporting carrier proteins (e.g., slc6a20) that are predominantly expressed in the small intestine or kidney rather than the liver.

scholarly journals Cerebrospinal Fluid and Interstitial Fluid Motion via the Glymphatic Pathway Modelled by Optimal Mass Transport

2016 ◽  
Author(s):  
Vadim Ratner ◽  
Yi Gao ◽  
Hedok Lee ◽  
Maikan Nedergaard ◽  
Helene Benveniste ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Interstitial Fluid ◽  
Initial Conditions ◽  
Fluid Motion ◽  
Flow Patterns ◽  
Brain Parenchyma ◽  
Fluid Exchange ◽  
Waste Products ◽  
Glymphatic Pathway ◽  
The Brain

It was recently shown that the brain-wide cerebrospinal fluid (CSF) and interstitial fluid exchange system designated the `glymphatic pathway' plays a key role in removing waste products from the brain, similarly to the lymphatic system in other body organs [1,2]. It is therefore important to study the flow patterns of glymphatic transport through the live brain in order to better understand its functionality in normal and pathological states. Unlike blood, the CSF does not flow rapidly through a network of dedicated vessels, but rather through peri-vascular channels and brain parenchyma in a slower time-domain, and thus conventional fMRI or other blood-flow sensitive MRI sequences do not provide much useful information about the desired flow patterns. We have accordingly analyzed a series of MRI images, taken at different times, of the brain of a live rat, which was injected with a paramagnetic tracer into the CSF via the lumbar intrathecal space of the spine. Our goal is twofold: (a) find glymphatic (tracer) flow directions in the live rodent brain; and (b) provide a model of a (healthy) brain that will allow the prediction of tracer concentrations given initial conditions. We model the liquid flow through the brain by the diffusion equation. We then use the Optimal Mass Transfer (OMT) approach [3] to model the glymphatic flow vector field, and estimate the diffusion tensors by analyzing the (changes in the) flow. Simulations show that the resulting model successfully reproduces the dominant features of the experimental data.

scholarly journals The Pharmacology of Xenobiotics after Intracerebro Spinal Fluid Administration: Implications for the Treatment of Brain Tumors

2021 ◽  
Vol 22 (3) ◽  
pp. 1281
Author(s):  
Justine Paris ◽  
Eurydice Angeli ◽  
Guilhem Bousquet
Keyword(s):  
Cerebrospinal Fluid ◽  
Brain Metastasis ◽  
Poor Prognosis ◽  
Drug Distribution ◽  
Molecular Targets ◽  
Intrathecal Administration ◽  
Brain Parenchyma ◽  
Brain Distribution ◽  
Improvement In Survival ◽  
The Brain

The incidence of brain metastasis has been increasing for 10 years, with poor prognosis, unlike the improvement in survival for extracranial tumor localizations. Since recent advances in molecular biology and the development of specific molecular targets, knowledge of the brain distribution of drugs has become a pharmaceutical challenge. Most anticancer drugs fail to cross the blood–brain barrier. In order to get around this problem and penetrate the brain parenchyma, the use of intrathecal administration has been developed, but the mechanisms governing drug distribution from the cerebrospinal fluid to the brain parenchyma are poorly understood. Thus, in this review we discuss the pharmacokinetics of drugs after intrathecal administration, their penetration of the brain parenchyma and the different systems causing their efflux from the brain to the blood.

scholarly journals Leukocyte Recruitment in the Cerebrospinal Fluid of Mice with Experimental Meningitis Is Inhibited by an Antibody to Junctional Adhesion Molecule (Jam)

1999 ◽  
Vol 190 (9) ◽  
pp. 1351-1356 ◽  
Author(s):  
Aldo Del Maschio ◽  
Ada De Luigi ◽  
Ines Martin-Padura ◽  
Manfred Brockhaus ◽  
Tamas Bartfai ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Adhesion Molecule ◽  
Brain Parenchyma ◽  
Immunoglobulin Superfamily ◽  
Leukocyte Transmigration ◽  
Leukocyte Accumulation ◽  
Brain Barrier Permeability ◽  
The Brain

The mechanisms that govern leukocyte transmigration through the endothelium are not yet fully defined. Junctional adhesion molecule (JAM) is a newly cloned member of the immunoglobulin superfamily which is selectively concentrated at tight junctions of endothelial and epithelial cells. A blocking monoclonal antibody (BV11 mAb) directed to JAM was able to inhibit monocyte transmigration through endothelial cells in in vitro and in vivo chemotaxis assays. In this study, we report that BV11 administration was able to attenuate cytokine-induced meningitis in mice. The intravenous injection of BV11 mAb significantly inhibited leukocyte accumulation in the cerebrospinal fluid and infiltration in the brain parenchyma. Blood–brain barrier permeability was also reduced by the mAb. We conclude that JAM may be a new target in limiting the inflammatory response that accompanies meningitis.

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