Reactive gliosis and the multicellular response to CNS damage and disease. Joshua E. Burda and Michael V. Sofroniew. Department of Neurobiology and Brain Research Institute, University of California Los Angeles, Los Angeles, CA 90095-1763, USA. Abstract: The central nervous system (CNS) is prone to heterogeneous insults of diverse etiologies that elicit multifaceted responses. Acute and focal injuries trigger wound repair with tissue replacement. Diffuse and chronic diseases provoke gradually escalating tissue changes. The responses to CNS insults involve complex interactions among cells of numerous lineages and functions, including CNS intrinsic neural cells, CNS intrinsic non-neural cells, and CNS extrinsic cells that enter from the circulation. The contributions of diverse non-neuronal cell types to outcome after acute injury, or to the progression of chronic disease, are of increasing interest as the push towards understanding and ameliorating CNS afflictions accelerates. In some cases considerable information is available, in others, comparatively little, as examined and reviewed here. Introduction: A major goal of contemporary neuroscience is to understand and ameliorate a wide range of central nervous system (CNS) disorders. Towards this end, there is increasing interest in cellular and molecular mechanisms of CNS responses to damage, disease and repair. Neurons are the principal cells executing neural functions and have long dominated investigations into mechanisms underlying CNS disorders. Nevertheless, mounting evidence indicates that treating all types of CNS disorders will require a deeper understanding of how multicellular responses to injury and disease are triggered, evolve, resolve (or not) and impact on neuronal function. The ability to repair tissue damaged by injury is fundamental to vertebrate biology and central to survival. Evolutionary pressure is likely to have forged certain fundamental cellular and molecular responses to damage that are common across different tissues. The wound or injury response in skin has long served as a model system for dissecting mechanisms of tissue repair after acute focal tissue damage and has provided insight into core cellular and molecular interactions. In addition, organ-specific features exist. Organ-intrinsic cells that are specialized in inflammatory regulation and tissue repair are emerging as critical elements in organ-specific responses to insults. Organ-specific features apply particularly in the CNS, where glial cells, which maintain the cytoarchitecture and homeostatic regulation without which neurons could not function normally in healthy tissue, are also principal responders to CNS insults. Changes in glial cell function during responses to insults have the potential to impact markedly on neuronal interactions and CNS functions. CNS insults are caused by diverse etiologies that can elicit a wide range of responses. For example, acute and focal injuries trigger wound repair with tissue replacement, whereas diffuse and chronic diseases can trigger gradually escalating tissue changes. Analysis of similarities and differences in such responses can provide valuable insights. Cellular responses to CNS insults involve complex interactions among cells of numerous lineages and functions, including CNS intrinsic neural cells, CNS intrinsic non-neReactive gliosis and the multicellular response to CNS damage and disease. Joshua E. Burda and Michael V. Sofroniew. Department of Neurobiology and Brain Research Institute, University of California Los Angeles, Los Angeles, CA 90095-1763, USA. Abstract: The central nervous system (CNS) is prone to heterogeneous insults of diverse etiologies that elicit multifaceted responses. Acute and focal injuries trigger wound repair with tissue replacement. Diffuse and chronic diseases provoke gradually escalating tissue changes. The responses to CNS insults involve complex interactions among cells of numerous lineages and functions, including CNS intrinsic neural cells, CNS intrinsic non-neural cells, and CNS extrinsic cells that enter from the circulation. The contributions of diverse non-neuronal cell types to outcome after acute injury, or to the progression of chronic disease, are of increasing interest as the push towards understanding and ameliorating CNS afflictions accelerates. In some cases considerable information is available, in others, comparatively little, as examined and reviewed here. Introduction: A major goal of contemporary neuroscience is to understand and ameliorate a wide range of central nervous system (CNS) disorders. Towards this end, there is increasing interest in cellular and molecular mechanisms of CNS responses to damage, disease and repair. Neurons are the principal cells executing neural functions and have long dominated investigations into mechanisms underlying CNS disorders. Nevertheless, mounting evidence indicates that treating all types of CNS disorders will require a deeper understanding of how multicellular responses to injury and disease are triggered, evolve, resolve (or not) and impact on neuronal function. The ability to repair tissue damaged by injury is fundamental to vertebrate biology and central to survival. Evolutionary pressure is likely to have forged certain fundamental cellular and molecular responses to damage that are common across different tissues. The wound or injury response in skin has long served as a model system for dissecting mechanisms of tissue repair after acute focal tissue damage and has provided insight into core cellular and molecular interactions. In addition, organ-specific features exist. Organ-intrinsic cells that are specialized in inflammatory regulation and tissue repair are emerging as critical elements in organ-specific responses to insults. Organ-specific features apply particularly in the CNS, where glial cells, which maintain the cytoarchitecture and homeostatic regulation without which neurons could not function normally in healthy tissue, are also principal responders to CNS insults. Changes in glial cell function during responses to insults have the potential to impact markedly on neuronal interactions and CNS functions. CNS insults are caused by diverse etiologies that can elicit a wide range of responses. For example, acute and focal injuries trigger wound repair with tissue replacement, whereas diffuse and chronic diseases can trigger gradually escalating tissue changes. Analysis of similarities and differences in such responses can provide valuable insights. Cellular responses to CNS insults involve complex interactions among cells of numerous lineages and functions, including CNS intrinsic neural cells, CNS intrinsic non-ne