Diversity in Reactive Astrocytes

Normal astrocytes in the adult undergo hypertrophy and proliferation and transform into reactive astrocytes following many types of central nervous system (CNS) injury (1–5). This process is termed astrogliosis and may result in the formation of a glial scar. Morphological studies on astrogliosis by neuroanatomists and pathologists at the beginning of this century focused on the most florid examples encountered in the immediate vicinity of destructive lesions of the CNS, such as lacerations, infarcts, abscesses, and multiple sclerosis plaques (6). Accordingly, the criteria which became standard for defining the reactive state were astrocytic hypertrophy and mild to moderate proliferation, an elaboration of long, thick cytoplasmic processes and an increase in glial filaments composed of glial febrillary acidic protein (GFAP) (7). Duchesne et al. (8,9) were the first to draw attention to biochemical diversity in reactive astrocytes in four different models of CNS parenchymal injury. After a hiatus of a decade, there is now growing awareness that reactive astrocytes in different categories of CNS lesions are biochemically heterogeneous, largely as a result of detailed studies of the astroglial reaction in different experimental models of CNS injury (1), combined with the use of a panel of methods to detect GFAP and a number of other conventional and novel “astrocyte-specific” and companion biochemical markers (2,10). From these investigations it is evident that astrocytes do not respond in a stereotypic fashion to all forms of CNS insult, but rather are capable of a variety of types of response, as defined by qualitative, quantitative, temporal and spatial differences in the patterns of molecules which they elaborate in different types of parenchymal injury. This biochemical diversity in reactive astrocytes appears to largely depend on the nature of the CNS injury and the microenvironment of the injury site. Thus, in cellular and molecular terms it is no longer appropriate to hold to a single general definition of astrogliosis. In this chapter, we consider the likely combinations of “damage signals” and factors in different CNS pathologies that act to induce subtypes of reactive astrocytes. Finally, attention is directed to the future use for mechanistic studies of new and evolving cell culture models of reactive astrogliosis.