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Updated: Jan 5, 2026
Three-dimensional Confocal Analysis of Microglia/macrophage Markers of Polarization in Experimental Brain Injury
Published on: September 4, 2013
Fractalkine Modulates Microglia Metabolism in Brain Ischemia
Clotilde Lauro1, Giuseppina Chece1, Lucia Monaco1
1Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy.
Abstract:
In the CNS, the chemokine CX3CL1 (fractalkine) is expressed on neurons while its specific receptor CX3CR1 is expressed on microglia and macrophages. Microglia play an important role in health and disease through CX3CL1/CX3CR1 signaling, and in many neurodegenerative disorders, microglia dysregulation has been associated with neuro-inflammation. We have previously shown that CX3CL1 has neuroprotective effects against cerebral ischemia injury. Here, we investigated the involvement of CX3CL1 in the modulation of microglia phenotype and the underlying neuroprotective effect on ischemia injury. The expression profiles of anti- and pro-inflammatory genes showed that CX3CL1 markedly inhibited microglial activation both in vitro and in vivo after permanent middle cerebral artery occlusion (pMCAO), accompanied by an increase in the expression of anti-inflammatory genes. Moreover, CX3CL1 induces a metabolic switch in microglial cells with an increase in the expression of genes related to the oxidative pathway and a reduction in those related to the glycolytic pathway, which is the metabolic state associated to the pro-inflammatory phenotype for energy production. The data reported in this paper suggest that CX3CL1 protects against cerebral ischemia modulating the activation state of microglia and its metabolism in order to restrain inflammation and organize a neuroprotective response against the ischemic insult.
Insights
Chemokine CX3CL1 (fractalkine) protects the brain from stroke by reducing harmful microglial activation and inflammation. It shifts microglial metabolism, promoting a neuroprotective state against ischemic injury.
Area of Science:
- Neuroscience
- Immunology
- Molecular Biology
Background:
- Microglia, immune cells in the central nervous system (CNS), play a critical role in neurological health and disease.
- Dysregulation of microglia and neuro-inflammation are implicated in neurodegenerative disorders.
- The CX3CL1 (fractalkine) and CX3CR1 signaling pathway is crucial for microglia function.
Purpose of the Study:
- To investigate the role of CX3CL1 in modulating microglial phenotype.
- To elucidate the neuroprotective mechanisms of CX3CL1 against cerebral ischemia injury.
- To understand how CX3CL1 influences microglial metabolism and inflammatory responses.
Main Methods:
- Analysis of anti- and pro-inflammatory gene expression in microglia.
- In vitro and in vivo studies following permanent middle cerebral artery occlusion (pMCAO).
- Assessment of metabolic gene expression in microglial cells.
Main Results:
- CX3CL1 significantly inhibited microglial activation both in vitro and in vivo after pMCAO.
- CX3CL1 treatment increased the expression of anti-inflammatory genes in microglia.
- CX3CL1 induced a metabolic switch in microglia, favoring oxidative pathways over glycolytic pathways.
Conclusions:
- CX3CL1 exerts neuroprotective effects against cerebral ischemia by modulating microglial activation.
- CX3CL1 restrains inflammation by altering microglial metabolism towards a less inflammatory phenotype.
- This study highlights CX3CL1 as a potential therapeutic target for ischemic stroke.
