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Chemokine CCL2 Induces Apoptosis in Cortex Following Traumatic Brain Injury

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Abstract

The chemokine C-C motif ligand 2 (CCL2) is an important mediator of neuroinflammation. Released in response to acute injury, ischemia, and neurodegenerative disease, CCL2 binds primarily to the G-protein-coupled chemokine C-C motif receptor 2 (CCR2) to recruit inflammatory cells to sites of tissue damage. Inflammation is thought to have both beneficial and deleterious consequences following traumatic brain injury (TBI), so we investigated CCL2–CCR2 signaling during the post-TBI period to assess possible neurodegenerative and protective actions. Local TBI in adult rat cortex was induced by Feeney’s weight-drop method, and the expression of CCL2 and CCR2 in the tissue around the contusion site was measured by real-time quantitative PCR. Both CCL2 and CCR2 mRNA levels were increased markedly for at least 10 days after injury, peaking on day 3. The CCL2 protein was mainly co-localized with the astroglial marker glial fibrillary acidic protein and CCR2 protein with the neuronal nuclear marker NeuN as revealed by double immunofluorescence staining. A selective CCR2 antagonist, RS504393, reduced TUNEL staining, a marker of apoptosis, and improved performance in the Morris water maze 3 days post-TBI, suggesting that CCL2–CCR2 signaling has deleterious effects on neuronal survival and learning. Targeting the CCL2–CCR2 pathway may provide a novel therapeutic approach for the treatment of TBI.

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Abbreviations

TBI:

Traumatic brain injury

CCL2:

Chemokine C-C motif ligand 2

CCR2:

Chemokine C-C motif receptor 2

NeuN:

Neuronal nuclei

GFAP:

Glial fibrillary acidic protein

GAPDH:

Glyceraldehyde-3-phosphate dehydrogenase

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Authors and Affiliations

  1. Nanjing Medical University, 140 HanZhong Road, Nanjing, Jiangsu Province, 210029, China

    Su Liu & Qinfeng Wu

  2. Department of Rehabilitation Medicine, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu Province, 210029, China

    Lixia Zhang, Qi Wu & Tong Wang

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  1. Su Liu
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  2. Lixia Zhang
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  3. Qinfeng Wu
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  4. Qi Wu
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  5. Tong Wang
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Correspondence to Tong Wang.

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Liu, S., Zhang, L., Wu, Q. et al. Chemokine CCL2 Induces Apoptosis in Cortex Following Traumatic Brain Injury. J Mol Neurosci 51, 1021–1029 (2013). https://doi.org/10.1007/s12031-013-0091-8

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  • DOI: https://doi.org/10.1007/s12031-013-0091-8

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