Acta Neuropathol (2010) 119:7–35 DOI 10.1007/s00401-009-0619-8 R E V I E W Astrocytes: biology and pathology Michael V. Sofroniew • Harry V. Vinters Received: 17 November 2009 / Revised: 23 November 2009 / Accepted: 24 November 2009 / Published online: 10 December 2009 The Author(s) 2009. This article is published with open access at Springerlink.com Abstract Astrocytes are specialized glial cells that out- number neurons by over ﬁvefold. They contiguously tile the entire central nervous system (CNS) and exert many essen- tial complex functions in the healthy CNS. Astrocytes respond to all forms of CNS insults through a process referred to as reactive astrogliosis, which has become a pathological hallmark of CNS structural lesions. Substantial progress has been made recently in determining functions and mechanisms of reactive astrogliosis and in identifying roles of astrocytes in CNS disorders and pathologies. A vast molecular arsenal at the disposal of reactive astrocytes is being deﬁned. Transgenic mouse models are dissecting speciﬁc aspects of reactive astrocytosis and glial scar formation in vivo. Astrocyte involvement in speciﬁc clinicopathological entities is being deﬁned. It is now clear that reactive astrogliosis is not a simple all-or-none phe- nomenon but is a ﬁnely gradated continuum of changes that occur in context-dependent manners regulated by speciﬁc signaling events. These changes range from reversible alterations in gene expression and cell hypertrophy with preservation of cellular domains and tissue structure, to long- lasting scar formation with rearrangement of tissue structure. M. V. Sofroniew (&) Department of Neurobiology, David Geffen School of Medicine, University of California, 10833 Le Conte Avenue, Los Angeles, CA 90095-1763, USA e-mail: sofroniew@mednet.ucla.edu H. V. Vinters Division of Neuropathology, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095-1763, USA H. V. Vinters Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095-1732, USA Increasing evidence points towards the potential of reactive astrogliosis to play either primary or contributing roles in CNS disorders via loss of normal astrocyte functions or gain of abnormal effects. This article reviews (1) astrocyte functions in healthy CNS, (2) mechanisms and functions of reactive astrogliosis and glial scar formation, and (3) ways in which reactive astrocytes may cause or contribute to speciﬁc CNS disorders and lesions. Keywords Astrocyte Reactive astrogliosis GFAP Pathology Central nervous system Glial scar Introduction Until quite recently, the prevailing view regarding the biol- ogy and pathology of astrocytes among those studying clinical disorders and structural lesions of the central nervous system (CNS) was most likely to be that (1) astrocytes are supportive glial cell components in neural tissue and (2) reactive astrogliosis is a reliable and sensitive marker of diseased tissue. The notion that dysfunctions of astrocytes or reactive astrocytes might contribute to the presentation of clinical signs or to mechanisms leading to pathological changes in CNS tissue was generally not considered. How- ever, this viewpoint is gradually changing as a result of steadily increasing interest in and study of the biology and pathology of astrocytes. Over the past 25 years it has become clear that astrocytes are responsible for a wide variety of complex and essential functions in the healthy CNS, including primary roles in synaptic transmission and infor- mation processing by neural circuit functions. The functions and mechanisms of reactive astrogliosis and glial scar for- mation are gradually being elucidated. There is a growing body of evidence that points towards the potential for loss of 123