Schematic representations that summarize different gradations of reactive astrogliosis. a Astrocytes in healthy CNS tissue. b Mild to moderate reactive astrogliosis comprises variable changes in molecular expression and functional activity together with variable degrees of cellular hypertrophy. Such changes occur after mild trauma or at sites distant from a more severe injury, or after moderate metabolic or molecular insults or milder infections or inflammatory activation. These changes vary with insult severity, involve little anatomical overlap of the processes of neighboring astrocytes and exhibit the potential for structural resolution if the triggering insult is removed or resolves. c Severe diffuse reactive astrogliosis includes changes in molecular expression, functional activity and cellular hypertrophy, as well newly proliferated astrocytes (with red nuclei in figure), disrupting astrocyte domains and causing long-lasting reorganization of tissue architecture. Such changes are found in areas surrounding severe focal lesions, infections or areas responding to chronic neurodegenerative triggers. d Severe reactive astrogliosis with compact glial scar formation occurs along borders to areas of overt tissue damage and inflammation, and includes newly proliferated astrocytes (with red nuclei in figure) and other cell types (gray in figure) such as fibromeningeal cells and other glia, as well as deposition of dense collagenous extracellular matrix. In the compact glial scar, astrocytes have densely overlapping processes. Mature glial scars tend to persist for long periods and act as barriers not only to axon regeneration but also to inflammatory cells, infectious agents, and non-CNS cells in a manner that protects healthy tissue from nearby areas of intense inflammation