White paper on astrocytes in diseases of the central nervous system

Astrocytes are a type of cell in the central nervous system (CNS) with homeostatic and computational roles in neural circuits. Hypertrophy of astrocytes was recognized in the mid XIXth century as an almost universal sign of CNS pathology, and the term ‘reactive astrocytes’ was coined to describe astrocytic remodeling in response to pathologic conditions. In the decade of the 90s of the XXth century, the study of reactive astrocytes exploded as part of the so-called ‘neuroinflammation’ in CNS pathologies; however, thirty years later the field is stagnated. There are no therapies derived from research on ‘inflammatory’ astrocytes, data from highly influential studies cannot be reproduced, and, importantly, astrocyte experts do not agree on basic issues including what reactive astrocytes are. A few of us capitalized on this discontent by fostering a necessary debate. The result is a working consensus of 80+ authors on reactive astrocytes. We take positions on controversies regarding the impact of astrocytes in CNS diseases, we discuss nomenclature, provide definitions, and we outline a systematic approach to unraveling the contribution of astrocytes to disorders of the CNS aging. This article is expected to inform clinical thinking and research on astrocytes and to promote the development of astrocyte-based biomarkers and therapies.