Role of CCL2 (MCP-1) in traumatic brain injury (TBI): evidence from severe TBI patients and CCL2-/- mice

Semple, Bridgette D; Bye, Nicole; Rancan, Mario; Ziebell, Jenna M; Morganti-Kossmann, M Cristina

doi:10.1038/jcbfm.2009.262

Cited by 358Traumatic Brain Injury and Neurovascular DisturbancesTraumatic Brain Injury ResearchAutomotive and Human Injury Biomechanics

Role of CCL2 (MCP-1) in traumatic brain injury (TBI): evidence from severe TBI patients and CCL2-/- mice

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Semple, Bridgette D, Bye, Nicole, Rancan, Mario, Ziebell, Jenna M, Morganti-Kossmann, M Cristina·2010·Journal of Cerebral Blood Flow & Metabolism

DOI 10.1038/jcbfm.2009.262PMC PMC2949175

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Abstract

Cerebral inflammation involves molecular cascades contributing to progressive damage after traumatic brain injury (TBI). The chemokine CC ligand-2 (CCL2) (formerly monocyte chemoattractant protein-1, MCP-1) is implicated in macrophage recruitment into damaged parenchyma after TBI. This study analyzed the presence of CCL2 in human TBI, and further investigated the role of CCL2 in physiological and cellular mechanisms of secondary brain damage after TBI. Sustained elevation of CCL2 was detected in the cerebrospinal fluid (CSF) of severe TBI patients for 10 days after trauma, and in cortical homogenates of C57Bl/6 mice, peaking at 4 to 12 h after closed head injury (CHI). Neurological outcome, lesion volume, macrophage/microglia infiltration, astrogliosis, and the cerebral cytokine network were thus examined in CCL2-deficient (−/−) mice subjected to CHI. We found that CCL2−/− mice showed altered production of multiple cytokines acutely (2 to 24 h); however, this did not affect lesion size or cell death within the first week after CHI. In contrast, by 2 and 4 weeks, a delayed reduction in lesion volume, macrophage accumulation, and astrogliosis were observed in the injured cortex and ipsilateral thalamus of CCL2−/− mice, corresponding to improved functional recovery as compared with wild-type mice after CHI. Our findings confirm the significant role of CCL2 in mediating post-traumatic secondary brain damage.

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Genetic deletion of CCL2 attenuates lesion volume, reduces macrophage recruitment and astrogliosis, and improves functional outcome compared to controls after CHI.
“Genetic deletion of CC ligand-2 (CCL2), the cognate ligand for CCR2, attenuates lesion volume, reduces macrophage recruitment and astrogliosis, and improves functional outcome compared to controls after CHI (60).”
From The Inflammatory Continuum of Traumatic Brain Injury and Alzheimer’s Disease (2018) · cites this paper as [60]

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Anatomical and Functional Outcomes following a Precise, Graded, Dorsal Laceration Spinal Cord Injury in C57BL/6 Mice
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Hellewell, S. C., Semple, B. D., & Morganti-Kossmann, M. C. (2015) · Brain Research · doi:10.1016/j.brainres.2015.12.024 · Cited by 92 · see citing works
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CCL2 is associated with microglia and macrophage recruitment in chronic traumatic encephalopathy
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BackgroundInfluential
Recombinant human interleukin-1 receptor antagonist promotes M1 microglia biased cytokines and chemokines following human traumatic brain injury
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Diffuse Brain Injury Induces Acute Post-Traumatic Sleep
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BackgroundSelf-citation
Small extracellular vesicles encapsulating CCL2 from activated astrocytes induce microglial activation and neuronal apoptosis after traumatic spinal cord injury
Rong, Y., Ji, C., Wang, Z., Ge, X., Wang, J., Wu, Y., Tang, P., Jiang, D., Fan, J., Yin, G., et al. (2021) · Journal of Neuroinflammation · doi:10.1186/s12974-021-02268-y · Cited by 96 · see citing works
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Sun, M., Brady, R. D., Wright, D. K., Kim, H. A., Zhang, S. R., Sobey, C. G., Johnstone, M. R., O'Brien, T. J., Semple, B. D., McDonald, S. J., et al. (2017) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2017.08.005 · Cited by 79 · see citing works
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Posttraumatic therapeutic hypothermia alters microglial and macrophage polarization toward a beneficial phenotype
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Knockout of ccr2 alleviates photoreceptor cell death in a model of retinitis pigmentosa
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Background
CCL2 modulates cytokine production in cultured mouse astrocytes
Semple, B., Frugier, T., & Morganti-Kossmann, M. (2010) · Journal of Neuroinflammation · doi:10.1186/1742-2094-7-67 · Cited by 72 · see citing works
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The Temporal Expression, Cellular Localization, and Inhibition of the Chemokines MIP-2 and MCP-1 after Traumatic Brain Injury in the Rat
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Authors: Semple, B. D., Bye, N., Rancan, M., Ziebell, J. M., & Morganti-Kossmann, M. C.
Affiliations: The Alfred Hospital (AU)
Triemli Hospital (CH)
Corresponding author: Morganti-Kossmann, M Cristina
ORCID: Semple, Bridgette D
Bye, Nicole
Ziebell, Jenna M
Morganti-Kossmann, M Cristina
Venue: Journal of Cerebral Blood Flow & Metabolism
Publisher: SAGE Publications
Published: 2009-12-23
Volume: 30
Issue: 4
Pages: 769-782
ISSN: 0271-678X (ISSN-L)
1559-7016
DOI: 10.1038/jcbfm.2009.262
PMC: PMC2949175
OpenAlex: W2159744238
Cited by: 358
References: 0
Citations by year: 2026: 8 · 2025: 21 · 2024: 24 · 2023: 17 · 2022: 29 · 2021: 20 · 2020: 25 · 2019: 18 · 2018: 25 · 2017: 20 · 2016: 29 · 2015: 25 · 2014: 27 · 2013: 23 · 2012: 23
FWCI: 10.00
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: journals.sagepub.com/page/policies/text-and-data-mining-license (tdm)
Locations: Journal of Cerebral Blood Flow & Metabolism (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
eCite Digital Repository (University of Tasmania) (submittedVersion)
Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
Figshare (submittedVersion)
Funders: Universitätsspital Zürich
Topics: Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Automotive and Human Injury Biomechanics
Keywords: MCP-1, traumatic brain injury, chemokines, secondary brain injury, macrophage recruitment, microglia, astrocyte activation, cerebrospinal fluid biomarkers, closed head injury, neuroinflammation, lesion volume, functional recovery, cytokines
MeSH terms: Animals, Brain, Brain Injuries, Gliosis, Humans, Inflammation, Macrophages, Mice, Inbred C57BL, Biomarkers, Cytokines, Mice, Knockout, Chemokine CCL2, In Situ Nick-End Labeling, Mice, Receptors, CCR2

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Role of CCL2 (MCP-1) in traumatic brain injury (TBI): evidence from severe TBI patients and CCL2-/- mice

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