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Pain and Therapy

Open Access 14-05-2024 | Migraine | REVIEW

The Role of Astrocytes in Migraine with Cortical Spreading Depression: Protagonists or Bystanders? A Narrative Review

Authors: Meng-fan Yang, Dong-xue Ren, Xue Pan, Chang-xin Li, Sui-yi Xu

Published in: Pain and Therapy

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Abstract

Cortical spreading depression (CSD) is a slow wave of cortical depolarization closely associated with migraines with an aura. Previously, it was thought that CSD depolarization was mainly driven by neurons, with characteristic changes in neuronal swelling and increased extracellular potassium (K+) and glutamate. However, the role of astrocytes, a member of the neurovascular unit, in migraine with CSD has recently received increasing attention. In the early stages of CSD, astrocytes provide neurons with energy support and clear K+ and glutamate from synaptic gaps. However, in the late stages of CSD, astrocytes release large amounts of lactic acid to exacerbate hypoxia when the energy demand exceeds the astrocytes’ compensatory capacity. Astrocyte endfoot swelling is a characteristic of CSD, and neurons are not similarly altered. It is primarily due to K+ influx and abnormally active calcium (Ca2+) signaling. Aquaporin 4 (AQP-4) only mediates K+ influx and has little role as an aquaporin. Astrocytes endfoot swelling causes perivascular space closure, slowing the glymphatic system flow and exacerbating neuroinflammation, leading to persistent CSD. Astrocytes are double-edged swords in migraine with CSD and may be potential targets for CSD interventions.
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Metadata
Title
The Role of Astrocytes in Migraine with Cortical Spreading Depression: Protagonists or Bystanders? A Narrative Review
Authors
Meng-fan Yang
Dong-xue Ren
Xue Pan
Chang-xin Li
Sui-yi Xu
Publication date
14-05-2024
Publisher
Springer Healthcare
Published in
Pain and Therapy
Print ISSN: 2193-8237
Electronic ISSN: 2193-651X
DOI
https://doi.org/10.1007/s40122-024-00610-9
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