Reactive astrocyte nomenclature, definitions, and future directions

Reactive astrocytes are astrocytes that change their morphology, molecular makeup, and function in response to injury, disease, or infection in the central nervous system (CNS). These changes have been observed for over a century, but their exact role in CNS diseases, repair processes, and aging remains unclear. The article argues against simple classifications of reactive astrocytes as either 'good' or 'bad,' 'neurotoxic' or 'neuroprotective,' or 'A1' versus 'A2.' Instead, it suggests a more comprehensive approach that considers multiple molecular and functional characteristics, preferably in living organisms. The authors propose guidelines for research on reactive astrocytes, including assessing multiple parameters, using multivariate statistics, and determining their impact on pathological hallmarks in relevant models. This approach may lead to the discovery of astrocyte-based biomarkers and therapies that can modulate the actions of reactive astrocytes.

• 1
  Reactive astrocytes engage in molecularly defined programs involving changes in transcriptional regulation, biochemical, morphological, metabolic, and physiological remodeling, resulting in altered function.
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  GFAP upregulation is a common but not absolute marker of reactive astrocyte remodeling and does not strictly correlate with the extent thereof or indicate altered functions.
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  Transcriptomic studies reveal that reactive astrocytes adopt distinct molecular states in different disease models, CNS regions, and brain tumors, suggesting complex functional changes.