ArticlePloS one2011
Spreading depression sends microglia on Lévy flights.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 93 citations in OpenAlex.
- Non-neuronal targets for migraine therapy.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Review
- Targeting glial-orchestrated neuroinflammation in migraine pathophysiology.The journal of headache and pain · 2026Review
- The mysterious link between migraine aura and migraine headache.PLoS biology · 2025Article
- The link between spreading depolarization and innate immunity in the central nervous system.The journal of headache and pain · 2025Review
- Unraveling the interplay of neuroinflammatory signaling between parenchymal and meningeal cells in migraine headache.The journal of headache and pain · 2024Review
- Cranial irradiation disrupts homeostatic microglial dynamic behavior.Journal of neuroinflammation · 2024Article
- Increased CX3CL1 in cerebrospinal fluid and ictal serum t-tau elevations in migraine: results from a cross-sectional exploratory case-control study.The journal of headache and pain · 2024Article
- History of Microglia.Advances in neurobiology · 2024Article
- Vesicular HMGB1 release from neurons stressed with spreading depolarization enables confined inflammatory signaling to astrocytes.Journal of neuroinflammation · 2023Article
- A Dynamic Balance between Neuronal Death and Clearance in anThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- The Role of Glial Cells in Different Phases of Migraine: Lessons from Preclinical Studies.International journal of molecular sciences · 2023Review
- Glia Signaling and Brain Microenvironment in Migraine.Molecular neurobiology · 2023Review
- Cortical Spreading Depolarization and Delayed Cerebral Ischemia; Rethinking Secondary Neurological Injury in Subarachnoid Hemorrhage.International journal of molecular sciences · 2023Review
- Parenchymal neuroinflammatory signaling and dural neurogenic inflammation in migraine.The journal of headache and pain · 2021Review
- Article
- Environmental Enrichment and Its Benefits for Migraine: Dendritic Cell Extracellular Vesicles as an Effective Mimetic.Journal of cellular immunology · 2021Article
- Microglia alter the threshold of spreading depolarization and related potassium uptake in the mouse brain.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2020Article
- P2YGlia · 2020Article
- Microglia: Lifelong patrolling immune cells of the brain.Progress in neurobiology · 2019Review
- Effects of the ecto-ATPase apyrase on microglial ramification and surveillance reflect cell depolarization, not ATP depletion.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Spreading depression (SD) is thought to cause migraine aura, and perhaps migraine, and includes a transient loss of synaptic activity preceded and followed by increased neuronal excitability. Activated microglia influence neuronal activity and play an important role in homeostatic synaptic scaling via release of cytokines. Furthermore, enhanced neuronal function activates microglia to not only secrete cytokines but also to increase the motility of their branches, with somata remaining stationary. While SD also increases the release of cytokines from microglia, the effects on microglial movement from its synaptic activity fluctuations are unknown. Accordingly, we used time-lapse imaging of rat hippocampal slice cultures to probe for microglial movement associated with SD. We observed that in uninjured brain whole microglial cells moved. The movements were well described by the type of Lévy flight known to be associated with an optimal search pattern. Hours after SD, when synaptic activity rose, microglial cell movement was significantly increased. To test how synaptic activity influenced microglial movement, we enhanced neuronal activity with chemical long-term potentiation or LPS and abolished it with TTX. We found that microglial movement was significantly decreased by enhanced neuronal activity and significantly increased by activity blockade. Finally, application of glutamate and ATP to mimic restoration of synaptic activity in the presence of TTX stopped microglial movement that was otherwise seen with TTX. Thus, synaptic activity retains microglial cells in place and an absence of synaptic activity sends them off to influence wider expanses of brain. Perhaps increased microglial movements after SD are a long-lasting, and thus maladaptive, response in which these cells increase neuronal activity via contact or paracrine signaling, which results in increased susceptibility of larger brain areas to SD. If true, then targeting mechanisms that retard activity-dependent microglial Lévy flights may be a novel means to reduce susceptibility to migraine.
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