Glial scar: An Overview
Glial scar formation (gliosis) is a reactive cellular process involving astrogliosis that occurs after injury to the central nervous system. As with scarring in other organs and tissues, the glial scar is the body's mechanism to protect and begin the healing process in the nervous system.
In the context of neurodegeneration, formation of the glial scar has been shown to have both beneficial and detrimental effects. Particularly, many neuro-developmental inhibitor molecules are secreted by the cells within the scar that prevent complete physical and functional recovery of the central nervous system after injury or disease. On the other hand, absence of the glial scar has been associated with impairments in the repair of the blood brain barrier.
Reactive astrocytes are the main cellular component of the glial scar. After injury, astrocytes undergo morphological changes, extend their processes, and increase synthesis of glial fibrillary acidic protein (GFAP). GFAP is an important intermediate filament protein that allows the astrocytes to begin synthesizing more cytoskeletal supportive structures and extend pseudopodia. Ultimately, the astrocytes form a dense web of their plasma membrane extensions that fills the empty space generated by the dead or dying neuronal cells (a process called astrogliosis). The heavy proliferation of astrocytes also modifies the extracellular matrix surrounding the damaged region by secreting many molecules including laminin, fibronectin, tenascin C, and proteoglycans. These molecules are important modulators of neuronal outgrowth. Accordingly, their presence after injury contributes to inhibition of regeneration. Another important caveat of the astrocytic response to CNS injuries is its heterogeneity. Particularly, the response of the astrocytes to the injury varies depending on factors such as the nature of the injury and the microenvironment at the injury location. Further, the reactive astrocytes in the immediate vicinity of the injury increase gene expression, thus compounding the response of other astrocytes and contributing to the heterogeneity. Particularly, astrocytes closest to the lesion generally secrete more inhibitory molecules into the extracellular matrix.
Microglia are the second most prominent cell type present within the glial scar. They are the nervous system analog of immune system macrophages. Microglia rapidly activate near the injury and secrete several cytokines, bioactive lipids, coagulation factors, reactive oxygen intermediates, and neurotrophic factors. The expression of these molecules depends on the location of the microglial cells relative to the injury, with the cells closest to the injury secreting the largest amount of such biologically active molecules.
Endothelial cells and fibroblasts
The various biologically active molecules secreted by microglia stimulate and recruit endothelial cells and fibroblasts. These cells help stimulate angiogenesis and collagen secretion into the injured area. Ultimately, the amount of capillaries extended into the injured area is twice that of uninjured central nervous system regions.
The basal membrane is a histopathological extracellular matrix feature that forms at the center of injury and partially covers the astrocytic processes. It is composed of three layers with the basal lamina as the prominent layer. Molecularly, the basal membrane is created by glycoprotein and proteoglycan protomers. Further, two independent networks are formed within the basal membrane by collagen IV and laminin for structural support. Other molecular components of the basal membrane include fibulin-1, fibronectin, entactin, and heparin sulfate proteoglycan perlecan. Ultimately, the astrocytes attach to the basal membrane, and the complex surrounds the blood vessels and nervous tissue to form the initial wound covering.
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Journal of Clinical & Experimental Neuroimmunology