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.

Item Type:	Refereed Article
Keywords:	brain trauma, chemokines, inflammation, macrophages
Research Division:	Biomedical and Clinical Sciences
Research Group:	Neurosciences
Research Field:	Neurosciences not elsewhere classified
Objective Division:	Health
Objective Group:	Clinical health
Objective Field:	Clinical health not elsewhere classified
UTAS Author:	Ziebell, JM (Dr Jenna Ziebell)
ID Code:	101706
Year Published:	2010
Web of Science® Times Cited:	205
Deposited By:	Wicking Dementia Research and Education Centre
Deposited On:	2015-07-02
Last Modified:	2015-09-28
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