The Temporal Expression, Cellular Localization, and Inhibition of the Chemokines MIP-2 and MCP-1 after Traumatic Brain Injury in the Rat

Jonathan K. J. Rhodes, John Sharkey, Peter J. D. Andrews

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    Abstract

    The expression of the neutrophil chemokine macrophage inflammatory protein-2 (MIP-2/CXCL2) and the monocyte chemokine monocyte chemotactic protein-1 (MCP-1/CCL2) have been described in glial cells in vitro but their origin following TBI has not been established. Furthermore, little is known of the modulation of these chemokines.

    Chemokine expression was investigated in male Sprague-Dawley rats following moderate lateral fluid percussion injury (LFPI). At 0, 4, 8, 12, and 24 h after injury, brains were harvested and MIP-2/CXCL2 and MCP=1/CCL2 levels measured by ELISA. To investigate the inhibition of chemokine expression a second cohort of animals received dexamethasone (1-15 mg/kg), FK506 (1 mg/kg), or vehicle, systemically, immediately after injury. These animals were sacrificed at the time of peak chemokine expression. A third cohort of animals was also sacrificed at the time of peak chemokine expression and immunohistochemistry performed for MIP-2/CXCL2 and MCP-1/CCL2.

    Following LFPI, chemokines were increased in the ipsilateral hemisphere, MIP-2/CXCL2 peaking at 4 h and MCP-1/CCL2 peaking at 8-12 h post-injury. Dexamethasone significantly reduced cortical MCP-1/CCL2, but not MIP-2/CXCL2 concentrations. FK506 did not inhibit chemokine expression. In undamaged brain, chemokine expression was localized to cells with a neuronal morphology. For MIP-2/CXCL2 this was supported by double staining for the neuronal antigen NeuN. In contused tissue, increased MIP-2/CXCL2 and MCP-1/CCL2 staining was visible in cells with the morphology of degenerating neurons.

    MIP-2/CXCL2 and MCP-1/CCL2 are increased after injury, and neurons appear to be the source of this expression. Chemokine expression was selectively inhibited by dexamethasone. The implications of this are discussed.

    Original languageEnglish
    Pages (from-to)507-525
    Number of pages19
    JournalJournal of Neurotrauma
    Volume26
    Issue number4
    DOIs
    Publication statusPublished - Apr 2009

    Keywords

    • brain
    • MCP-1/CCL2
    • MIP-2/CXCL2
    • trauma
    • MONOCYTE CHEMOATTRACTANT PROTEIN-1
    • CENTRAL-NERVOUS-SYSTEM
    • EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS
    • MACROPHAGE INFLAMMATORY PROTEIN-2
    • MICROVASCULAR ENDOTHELIAL-CELLS
    • FACTOR-KAPPA-B
    • MESSENGER-RNA
    • AXONAL INJURY
    • GLIAL-CELLS
    • CYCLOSPORINE-A

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