scholarly journals Microglia as hackers of the matrix: sculpting synapses and the extracellular space

Author(s):  
Joshua D. Crapser ◽  
Miguel A. Arreola ◽  
Kate I. Tsourmas ◽  
Kim N. Green

AbstractMicroglia shape the synaptic environment in health and disease, but synapses do not exist in a vacuum. Instead, pre- and postsynaptic terminals are surrounded by extracellular matrix (ECM), which together with glia comprise the four elements of the contemporary tetrapartite synapse model. While research in this area is still just beginning, accumulating evidence points toward a novel role for microglia in regulating the ECM during normal brain homeostasis, and such processes may, in turn, become dysfunctional in disease. As it relates to synapses, microglia are reported to modify the perisynaptic matrix, which is the diffuse matrix that surrounds dendritic and axonal terminals, as well as perineuronal nets (PNNs), specialized reticular formations of compact ECM that enwrap neuronal subsets and stabilize proximal synapses. The interconnected relationship between synapses and the ECM in which they are embedded suggests that alterations in one structure necessarily affect the dynamics of the other, and microglia may need to sculpt the matrix to modify the synapses within. Here, we provide an overview of the microglial regulation of synapses, perisynaptic matrix, and PNNs, propose candidate mechanisms by which these structures may be modified, and present the implications of such modifications in normal brain homeostasis and in disease.

2020 ◽  
pp. 153537022097719
Author(s):  
Aric F Logsdon ◽  
Elizabeth M Rhea ◽  
May Reed ◽  
William A Banks ◽  
Michelle A Erickson

The blood–brain barrier (BBB) is a vital interface that supports normal brain functions. Endothelial cells (ECs) are the main component of the BBB and are highly specialized to govern the transfer of substances into brain. The EC lumen is enmeshed with an extracellular matrix (ECM), known as the endothelial glycocalyx layer (EGL). The lumen-facing EGL is primarily comprised of proteoglycans (PGs) and glycosaminoglycans (GAGs), which function as the first line of defense for blood-to-brain transfer of substances. Circulating factors must first penetrate the EGL before interacting with the EC. The abundance and composition of the PG and GAGs can dictate EGL function, and determine which circulating substances communicate with the ECs. The EGL can interact with circulating factors through physio-chemical interactions with the EC. Some disease states reveal a “thinning” of the EGL that may increase EC interactions with components of the systemic circulation and alter BBB function. EGL changes may also contribute to the cognitive complications of systemic diseases, such as sepsis and diabetes. For decades, researchers have measured how genetic and environmental factors influence the peripheral EGL constituents; however, much less is known about the neurovascular EGL. In this mini-review, we introduce components of the EGL and innovative ways to measure their abundance and composition that may contribute to BBB dysfunction.


2008 ◽  
Vol 88 (4) ◽  
pp. 1277-1340 ◽  
Author(s):  
Eva Syková ◽  
Charles Nicholson

Diffusion in the extracellular space (ECS) of the brain is constrained by the volume fraction and the tortuosity and a modified diffusion equation represents the transport behavior of many molecules in the brain. Deviations from the equation reveal loss of molecules across the blood-brain barrier, through cellular uptake, binding, or other mechanisms. Early diffusion measurements used radiolabeled sucrose and other tracers. Presently, the real-time iontophoresis (RTI) method is employed for small ions and the integrative optical imaging (IOI) method for fluorescent macromolecules, including dextrans or proteins. Theoretical models and simulations of the ECS have explored the influence of ECS geometry, effects of dead-space microdomains, extracellular matrix, and interaction of macromolecules with ECS channels. Extensive experimental studies with the RTI method employing the cation tetramethylammonium (TMA) in normal brain tissue show that the volume fraction of the ECS typically is ∼20% and the tortuosity is ∼1.6 (i.e., free diffusion coefficient of TMA is reduced by 2.6), although there are regional variations. These parameters change during development and aging. Diffusion properties have been characterized in several interventions, including brain stimulation, osmotic challenge, and knockout of extracellular matrix components. Measurements have also been made during ischemia, in models of Alzheimer's and Parkinson's diseases, and in human gliomas. Overall, these studies improve our conception of ECS structure and the roles of glia and extracellular matrix in modulating the ECS microenvironment. Knowledge of ECS diffusion properties is valuable in contexts ranging from understanding extrasynaptic volume transmission to the development of paradigms for drug delivery to the brain.


2019 ◽  
Vol 47 (5) ◽  
pp. 1543-1555 ◽  
Author(s):  
Maurizio Mongiat ◽  
Simone Buraschi ◽  
Eva Andreuzzi ◽  
Thomas Neill ◽  
Renato V. Iozzo

Abstract The extracellular matrix is a network of secreted macromolecules that provides a harmonious meshwork for the growth and homeostatic development of organisms. It conveys multiple signaling cascades affecting specific surface receptors that impact cell behavior. During cancer growth, this bioactive meshwork is remodeled and enriched in newly formed blood vessels, which provide nutrients and oxygen to the growing tumor cells. Remodeling of the tumor microenvironment leads to the formation of bioactive fragments that may have a distinct function from their parent molecules, and the balance among these factors directly influence cell viability and metastatic progression. Indeed, the matrix acts as a gatekeeper by regulating the access of cancer cells to nutrients. Here, we will critically evaluate the role of selected matrix constituents in regulating tumor angiogenesis and provide up-to-date information concerning their primary mechanisms of action.


2014 ◽  
Vol 6 (2) ◽  
pp. 46-51
Author(s):  
Galang Amanda Dwi P. ◽  
Gregorius Edwadr ◽  
Agus Zainal Arifin

Nowadays, a large number of information can not be reached by the reader because of the misclassification of text-based documents. The misclassified data can also make the readers obtain the wrong information. The method which is proposed by this paper is aiming to classify the documents into the correct group.  Each document will have a membership value in several different classes. The method will be used to find the degree of similarity between the two documents is the semantic similarity. In fact, there is no document that doesn’t have a relationship with the other but their relationship might be close to 0. This method calculates the similarity between two documents by taking into account the level of similarity of words and their synonyms. After all inter-document similarity values obtained, a matrix will be created. The matrix is then used as a semi-supervised factor. The output of this method is the value of the membership of each document, which must be one of the greatest membership value for each document which indicates where the documents are grouped. Classification result computed by the method shows a good value which is 90 %. Index Terms - Fuzzy co-clustering, Heuristic, Semantica Similiarity, Semi-supervised learning.


Author(s):  
Pavithra. S. ◽  
H. G. Gouda ◽  
Rajalakshmi M. G.

Agni is termed as Vaishwanara as it takes the person from Mruthyuloka to Swargaloka. It is an important factor and is equitant to Prana; is one among Dashaprana Ayatana. Agni in Shareera is present in different forms with different actions. It is the responsible factor for both health and disease; on the other hand the successful outcome of treatment is also dependant on Agni. Chikitsa (treatment) is the process of bestowing normalcy which is either brought by Shodhana (purificatory) or Shamana (palliative) Karma. Snehapana is a pre-operative procedure for Shodhana Chikitsa where in Sneha Dravya (medicated fat) is administered for attainment of Upasthita Dosha Avastha and further ease in elimination of the vitiated Doshas. Assessment of Dosha, Dushya, Vyadhi Avastha, Roga Bala, Rogi Bala, Agni, Koshta etc. factors are essential for the attainment of Chikitsa Phala. Assessment of Agni not only helps in understanding Vyadhi but also enables to plan the dosage of Sneha to be administered. Thus this paper is an attempt to throw light on the importance of Agni, assessment of Agni and Agni Bala prior to Shodhananga Snehapana.


Blood ◽  
1987 ◽  
Vol 69 (5) ◽  
pp. 1531-1534 ◽  
Author(s):  
LA Sporn ◽  
VJ Marder ◽  
DD Wagner

Abstract Large multimers of von Willebrand factor (vWf) are released from the Weibel-Palade bodies of cultured endothelial cells following treatment with a secretagogue (Sporn et al, Cell 46:185, 1986). These multimers were shown by immunofluorescent staining to bind more extensively to the extracellular matrix of human foreskin fibroblasts than constitutively secreted vWf, which is composed predominantly of dimeric molecules. Increased binding of A23187-released vWf was not due to another component present in the releasate, since releasate from which vWf was adsorbed, when added together with constitutively secreted vWf, did not promote binding. When iodinated plasma vWf was overlaid onto the fibroblasts, the large forms bound preferentially to the matrix. These results indicated that the enhanced binding of the vWf released from the Weibel-Palade bodies was likely due to its large multimeric size. It appears that multivalency is an important component of vWf interaction with the extracellular matrix, just as has been shown for vWf interaction with platelets. The pool of vWf contained within the Weibel-Palade bodies, therefore, is not only especially suited for platelet binding, but also for interaction with the extracellular matrix.


1979 ◽  
Vol 58 (2_suppl) ◽  
pp. 922-929 ◽  
Author(s):  
M.U. Nylen

The literature on the ultrastructural morphology of the enamel matrix and its relationship to the crystals is reviewed. Two morphological entities of the matrix are discussed: One is the so-called stippled material which may be the initial cell product; the other, variously described as fibrillar, lamellar, tubular or helical, is thought by many to play a crucial role in nucleation and orientation of the crystals. A number of observations, however, suggest that the latter structures form secondarily to the crystals and that in reality they represent organic material adsorbed to the crystal surface and maintained as independent structures upon removal of the mineral. The need for additional studies is stressed including systematic studies of interactions between constituents of the organic matrix and the apatite crystals.


1991 ◽  
Vol 113 (4) ◽  
pp. 425-429 ◽  
Author(s):  
T. Hisatsune ◽  
T. Tabata ◽  
S. Masaki

Axisymmetric deformation of anisotropic porous materials caused by geometry of pores or by distribution of pores is analyzed. Two models of the materials are proposed: one consists of spherical cells each of which has a concentric ellipsoidal pore; and the other consists of ellipsoidal cells each of which has a concentric spherical pore. The velocity field in the matrix is assumed and the upper bound approach is attempted. Yield criteria are expressed as ellipses on the σm σ3 plane which are longer in longitudinal direction with increasing anisotropy and smaller with increasing volume fraction of the pore. Furthermore, the axes rotate about the origin at an angle α from the σm-axis, while the axis for isotropic porous materials is on the σm-axis.


2001 ◽  
Vol 12 (5) ◽  
pp. 373-398 ◽  
Author(s):  
Bjorn Steffensen ◽  
Lari Häkkinen ◽  
Hannu Larjava

During wound-healing, cells are required to migrate rapidly into the wound site via a proteolytically generated pathway in the provisional matrix, to produce new extracellular matrix, and, subsequently, to remodel the newly formed tissue matrix during the maturation phase. Two classes of molecules cooperate closely to achieve this goal, namely, the matrix adhesion and signaling receptors, the integrins, and matrix-degrading and -processing enzymes, the matrix metalloproteinases (MMPs). There is now substantial experimental evidence that blocking key molecules of either group will prevent or seriously delay wound-healing. It has been known for some time now that cell adhesion by means of the integrins regulates the expression of MMPs. In addition, certain MMPs can bind to integrins or other receptors on the cell surface involved in enzyme activation, thereby providing a mechanism for localized matrix degradation. By proteolytically modifying the existing matrix molecules, the MMPs can then induce changes in cell behavior and function from a state of rest to migration. During wound repair, the expression of integrins and MMPs is simultaneously up-regulated. This review will focus on those aspects of the extensive knowledge of fibroblast and keratinocyte MMPs and integrins in biological processes that relate to wound-healing.


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