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Sustained delivery of axon-specific growth factors not typically present in spinal cord lesions allows for robust axonal regrowth only if the astrocytic scar is present—a result that questions the prevailing dogma and suggests that astrocytic scarring aids rather than prevents central nervous system axon regeneration post injury.

Implantable biomaterials evoke foreign body responses in the central nervous system. The authors compare hydrogel-based biomaterials to identify cellular interactions and molecular mechanisms that drive different types of foreign body responses that have different effects on biomaterial function.

In this study, the authors show that altered medium spiny neuron excitability and symptom onset in Huntington's disease model mice is associated with decreased expression of Kir4.1 and impaired K⁺ handling by astrocytes. Exogenous expression of Kir4.1 could partially rescue motor function and prolong survival in HD mice.

Here the authors couple an integrative genomic analysis with substantial in vitro and in vivo experimental validation, identifying REST as a novel suppressor of a pro-regenerative gene program and CNS axon regeneration in mice.

The features of astrocytes surrounding CNS lesions are unclear. Here the authors show that after spinal cord injury or stroke in mice, mature astrocytes dedifferentiate, proliferate and are reprogrammed to adopt features of wound repair cells and form borders, re-establishing CNS integrity.

The Tabulae Paralytica, a compilation of four molecular atlases of spinal cord injury, provides a window into the pathobiology of spinal cord injury, establishing a framework for integrating multimodal, genome-scale measurements in four dimensions to study biology and medicine.

Transcriptional changes associated with astrocyte reactivity are highly heterogeneous and are customized from vast numbers of potential DEGs through context-specific combinatorial interactions amongst transcriptional regulators.

The central nervous system’s astrocyte cells respond to injury and disease. The finding that they form molecular memories of certain responses, and that these modify inflammatory signalling, sheds light on autommunity.

Astrocytes form borders that separate neural from non-neural tissue in both normal brain tissue and CNS lesions. In this Review, Michael Sofroniew discusses evidence that astrocytes along such borders have crucial roles in both attracting and restricting CNS inflammation, with important implications for diverse CNS disorders.

Stimulating the intrinsic growth capacity of neurons and providing growth-supportive substrate and chemoattraction can allow axon regrowth across anatomically complete spinal cord injuries in adult rodents.

Leng et al. establish CRISPRi screens in astrocytes to dissect pathways controlling inflammatory reactivity. They uncover two distinct inflammatory reactive signatures that are inversely regulated by STAT3 and validate that these exist in human disease.

This Review article by Baljit Khakh and Michael Sofroniew discusses the latest progress in demonstration of molecular, cellular and functional heterogeneity of astrocytes in the central nervous system. The article highlights the way in which this diversity within and across astrocytes can affect normal function of the brain differently, and discusses pathological conditions where astrocyte heterogeneity is instrumental in manifesting various aspects of CNS dysfunction.

Astrocytes, highly prevalent cells in the central nervous system, have been difficult to specifically target with adeno-associated viruses (AAVs). Here, the authors present a microRNA targeting cassette that de-targets other cells, increasing astrocyte specificity of AAVs to over 99%.

Astrocytes are emerging as causal or modulating factors in diverse neurological disorders. Two papers published in Nature Neuroscience in 2007 revealed astrocytes as causally contributing to motor neuron loss in amyotrophic lateral sclerosis, thereby challenging the longstanding neuron-centric view of neurodegenerative disease.

Fibrotic scarring after inflammation is well-characterized in peripheral tissues, but its role in the CNS is less clear. A new study shows that local proliferation of CNS fibroblasts drives fibrotic scar formation in response to circulating inflammatory cell infiltration in a model of multiple sclerosis, which may limit repair.

Inflammation of brain endothelial cells is seen in neurodegenerative conditions and in aging. Here the authors examine the role of astrocytes in blood brain barrier function using an iPSC-derived cell co-culture model.

Good–bad binary classifications fail to describe reactive astrocytes in CNS disorders. Here, 81 researchers reach consensus on widespread misconceptions and provide definitions and recommendations for future research on reactive astrocytes.

Disruption of the blood brain barrier can occur in several diseases. Here the authors show that targeted ablation of astrocytes results in a plasticity mechanism in nearby cells to maintain cerebrovascular coverage, but that this mechanism is impaired in older animals.

Spinal cord injury disrupts input from the brain to the spinal motor circuitry, but that circuitry and pattern generator circuits still exist below the lesion. A regime combining electrical and serotonergic agonist stimulation of the lesioned spinal cord with intensive treadmill training enabled rats to recover weight-bearing stepping that was very similar to normal walking.

A new study shows that a subset of the glia that express the proteoglycan NG2 can fire action potentials, contradicting the dogma that only neurons are excitable in the brain. These glia receive excitatory and inhibitory synaptic input, are selectively vulnerable to ischemia and are present into adulthood, though their function remains mysterious.

Understanding the role of astrocytic calcium signals has been hindered by our inability to measure calcium in small volume compartments. Here, the authors develop a technique to do this by modifying the genetically encoded calcium sensor GCaMP2 to ensure greater expression near the membrane.

Advances in cellular regeneration and technical approaches to spinal cord repair are on the verge of being translated into clinical trials.

After injury and in disease of the central nervous system (CNS), local cells called astrocytes respond with diverse molecular changes whose functional consequences are incompletely understood. A combined genomic and experimental analysis shows that classically-activated microglia, which are innate immune cells resident in CNS neural tissue, release molecules that drive astrocytes into a neurotoxic state, raising important questions about potential adaptive and maladaptive functions of such a mechanism.