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Matrix Metalloproteinases and Extracellular Matrix in the Central Nervous System
Introduction
Brain cells are surrounded by extracellular matrix (ECM) made up of large protein molecules. Interstitial fluid (ISF) moves between the cells and along perivascular spaces, mixing with the cerebrospinal fluid (CSF) to act as the lymph of the brain. Early investigators realized that a mechanism to remove waste products of metabolism and to deliver nutrients to the cells was essential, and they postulated the ISF/CSF, acting as a third circulation, performed this essential function. However, they had no idea of the size of the space and no way to visualize it until early electron micrographs showed a space between the cells, using a method of freeze substitution that preserved the water in the brain, demonstrating an appreciable extracellular space (ECS) .
Studies have revealed that the ECM is an essential component of the central nervous system (CNS). Estimated to comprise 15–20% of the brain tissue, its complex role in brain development and injury is beginning to emerge. ECM in the adult CNS is localized to three principal compartments: the basal lamina, the perineuronal nets (PNNs), and the neural interstitial matrix in the parenchyma ( http://www.nature.com/nrn/journal/v14/n10/full/nrn3550.html ) ( Fig. 61.1 ) . In the CNS, the basal lamina separates endothelial cells from parenchymal tissue and surrounds the pial surface; it is made up of collagen, laminin–nidogen (also known as entactin) complexes, fibronectin, dystroglycan, and perlecan. The basal lamina is a major site of action of the matrix-degrading metalloproteinases (MMPs), which act on the proteins in the basal lamina to disrupt the blood–brain barrier (BBB). The third component of the ECM is the interstitial matrix consisting of a dense network of proteoglycans, hyaluronan, tenascins, and link proteins.
![Figure 61.1, The three major compartments of the extracellular matrix (ECM) in the central nervous system (CNS). ECM components are arranged into basement membranes that lie outside cerebral vessels, condensed as perineuronal nets around the cell bodies and dendrites of neurons or diffusely distributed as the neural interstitial matrix between cells of the CNS parenchyma. The pink glial cells depict astrocytes, oligodendrocytes, or microglia [2] .](https://storage.googleapis.com/dl.dentistrykey.com/clinical/MatrixMetalloproteinasesandExtracellularMatrixintheCentralNervousSystem/0_3s20B9780128030585000618.jpg "Figure 61.1, The three major compartments of the extracellular matrix (ECM) in the central nervous system (CNS). ECM components are arranged into basement membranes that lie outside cerebral vessels, condensed as perineuronal nets around the cell bodies and dendrites of neurons or diffusely distributed as the neural interstitial matrix between cells of the CNS parenchyma. The pink glial cells depict astrocytes, oligodendrocytes, or microglia [2] .")
PNNs are a layer of lattice-like matrix that enwraps the surface of the soma and dendrites; they are mainly composed of hyaluronan, chondroitin sulfate proteoglycans (CSPG), link proteins, and tenascin R, and play a direct role in the control of CNS plasticity. Their removal is one way in which plasticity can be reactivated in the adult CNS .
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