Role of CX3CR1 (Fractalkine Receptor) in Brain Damage and Inflammation Induced by Focal Cerebral Ischemia in Mouse
Abstract
CX3CR1 (fractalkine receptor) is important for sustaining normal microglial activity in the brain. Lack of CX3CR1 reportedly results in neurotoxic microglial phenotype in disease models. The objective of this study was to test the hypothesis that the absence of CX3CR1 worsens the outcome in cerebral ischemia. We observed significantly smaller (56%) infarcts and blood-brain barrier damage in CX3CR1-deficient (CX3CR1-/-) animals compared with CX3CR1+/- and wild-type mice after transient occlusion of the middle cerebral artery (MCAo). Functional recovery of CX3CR1-/- animals was enhanced, while less number of apoptotic cells and infiltrating leukocytes were found in the ipsilateral hemisphere. Expression of IL-1beta mRNA, protein, and interleukin (IL)-1Ra and tumor necrosis factor (TNF)-alpha mRNAs was lower in CX3CR1-/- mice, whereas no difference was observed in the number of IL-1beta-expressing microglia or plasma IL-1beta concentration. We observed early IL-1beta expression in astrocytes in vivo after MCAo and after oxygen-glucose deprivation in vitro, which might contribute to the ischemic damage. Our findings indicate that lack of CX3CR1 does not result in microglial neurotoxicity after MCAo, but rather significantly reduces ischemic damage and inflammation. Reduced IL-1beta and TNFalpha expression as well as decreased leukocyte infiltration might be involved in the development of smaller infarcts in CX3CR1-/- animals.
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CX3CR1 deficiency ameliorates pathology in murine stroke models.
“In contrast , CX3CR1 deficiency ameliorates pathology in murine stroke models.”
From CX3CR1 Deficiency Alters Microglial Activation and Reduces Beta-Amyloid Deposition in Two Alzheimer's Disease Mouse Models (2010) · cites this paper as [19]
Cx3cr1 knockout mice exhibit smaller infarcts after transient middle cerebral artery occlusion.
“Indeed, the effect of CX3CR1 deficiency appears to depend on the nature of the CNS insult as recent studies demonstrated that Cx3cr1 knockout mice exhibit smaller infarcts after transient middle cerebral artery occlusion.19,20”
From CX3CR1 Deficiency Alters Microglial Activation and Reduces Beta-Amyloid Deposition in Two Alzheimer's Disease Mouse Models (2010) · cites this paper as [19]
The effect of CX3CR1 deficiency appears to depend on the nature of the CNS insult.
“Indeed, the effect of CX3CR1 deficiency appears to depend on the nature of the CNS insult as recent studies demonstrated that Cx3cr1 knockout mice exhibit smaller infarcts after transient middle cerebral artery occlusion.19,20”
From CX3CR1 Deficiency Alters Microglial Activation and Reduces Beta-Amyloid Deposition in Two Alzheimer's Disease Mouse Models (2010) · cites this paper as [19]
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- Authors
- Dénes, Á., Ferenczi, S., Halász, J., Környei, Z., & Kovács, K. J.
- Affiliations
- HUN-REN Institute of Experimental Medicine (HU)
- Fejér Megyei Szent György Egyetemi Oktató Kórház (HU)
- Corresponding author
- Dénes, Ádám
- Venue
- Journal of Cerebral Blood Flow & Metabolism
- Publisher
- SAGE Publications
- Published
- 2008-06-25
- Volume
- 28
- Issue
- 10
- Pages
- 1707-1721
- ISSN
- 0271-678X (ISSN-L)
- 1559-7016
- OpenAlex
- W2088542086
- Cited by
- 276
- References
- 6
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 12 · 2023: 7 · 2022: 12 · 2021: 14 · 2020: 6 · 2019: 12 · 2018: 19 · 2017: 19 · 2016: 19 · 2015: 28 · 2014: 29 · 2013: 22 · 2012: 21
- FWCI
- 10.08
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Cerebral Blood Flow & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- CX3CR1, focal cerebral ischemia, middle cerebral artery occlusion, neuroinflammation, microglia, infarct size, blood-brain barrier disruption, leukocyte infiltration, apoptosis, IL-1β, interleukin-1 receptor antagonist, TNF-α, astrocytes, oxygen-glucose deprivation
- MeSH terms
- CX3C Chemokine Receptor 1, Animals, Astrocytes, Blood-Brain Barrier, Cells, Cultured, Ischemic Attack, Transient, Encephalitis, Leukocytes, Male, Mice, Inbred C57BL, Neurons, Tumor Necrosis Factor-alpha, Apoptosis, Leukocyte Common Antigens, Microglia, Mice, Knockout, Receptors, Chemokine, Recovery of Function, Reverse Transcriptase Polymerase Chain Reaction, Infarction, Middle Cerebral Artery, Green Fluorescent Proteins, Mice, Interleukin-1beta
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