Reactive Astrocytes and Emerging Roles in Central Nervous System (CNS) Disorders
Open accessAbstract
In addition to their many functions in the healthy central nervous system (CNS), astrocytes respond to CNS damage and disease through a process called "reactivity." Recent evidence reveals that astrocyte reactivity is a heterogeneous spectrum of potential changes that occur in a context-specific manner. These changes are determined by diverse signaling events and vary not only with the nature and severity of different CNS insults but also with location in the CNS, genetic predispositions, age, and potentially also with "molecular memory" of previous reactivity events. Astrocyte reactivity can be associated with both essential beneficial functions as well as with harmful effects. The available information is rapidly expanding and much has been learned about molecular diversity of astrocyte reactivity. Emerging functional associations point toward central roles for astrocyte reactivity in determining the outcome in CNS disorders.
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Astrocytes recycle neurotransmitters, clear extracellular fluid potassium, contribute to synaptic plasticity and transmission, maintain the blood-brain barrier, release lactate to fuel neurons and axons, buffer free radicals, and regulate blood flow.
“Indeed, they recycle neurotransmitters, e.g., removing excessive glutamate through their glutamate transporters. Astrocytes clear extracellular fluid potassium, contribute to synaptic plasticity and transmission, maintain the BBB, release lactate to fuel neurons and axons, buffer free radicals, and regulate blood flow (reviewed in [398,399]).”
From Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy (2025) · cites this paper as [399]
The “Functions and Effects of Astrocyte Reactivity” section (page unavailable) identifies neurotransmitter reuptake and recycling and synapse stabilization as physiological functions. The “Reactive Astrocytes in Traumatic Injury and Stroke” section also says reactive astrocytes can influence synaptic plasticity. Our copy does not substantiate the remaining specific functions attributed here: extracellular potassium clearance, BBB maintenance, lactate fueling neurons and axons, free-radical buffering, or blood-flow regulation. (LLM, conf=0.88)
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References 135 · Cited by 55
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- Authors
- Liddelow, S. A., Olsen, M. L., & Sofroniew, M. V.
- Affiliations
- NYU Langone Health (US)
- Virginia Tech (US)
- University of California, Los Angeles (US)
- Venue
- Cold Spring Harbor Perspectives in Biology
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2024-02-05
- Volume
- 16
- Issue
- 7
- Pages
- a041356
- ISSN
- 1943-0264 (ISSN-L)
- OpenAlex
- W4391528693
- Cited by
- 55
- References
- 135
- Citations by year
- 2026: 12 · 2025: 32 · 2024: 11
- Type
- posted content
- Language
- en
- Open access
- Locations
- Cold Spring Harbor Perspectives in Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Keywords
- astrocyte activation, reactive astrocytes, central nervous system disorders, central nervous system injury, molecular memory, astrocyte signaling, neuroinflammation, disease outcome
- MeSH terms
- Animals, Astrocytes, Central Nervous System, Central Nervous System Diseases, Humans, Signal Transduction
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