Abstract
Abstract The inflammatory response after traumatic brain injury (TBI) contributes to neuronal death and progressive axonal loss to areas undamaged by the initial trauma. Moreover, anti-inflammatory therapies offer great hope to improve outcomes after TBI. Thus, it is important to find therapeutic targets to better control the inflammatory response after injury. In this study we used cells in culture, an animal model of TBI as well as brain and CSF samples obtained from patients with TBI to investigate, after injury, the role of the CLR family member, macrophage-inducible C-type lectin (mincle) in the production of the inflammatory cytokine TNF. Here we report that mincle is activated after TBI in both, humans and rodents. Our data show that moderate fluid percussion brain injury (using male Sprague-Dawley rats (250-350 g) subjected to moderate fluid-percussion brain injury (1.8-2.2 atm)) is associated with increase expression of SAP130, which activates mincle signaling resulting in phosphorylation of the enzyme syk. Moreover, we identified increased expression of SAP130 and mincle in cortical neurons after TBI. In addition, we show that SAP130 stimulates mincle signaling in primary neuronal cultures, resulting in increase expression of the inflammatory cytokine TNF. Acute TNF expression after TBI is associated with deleterious outcomes. In conclusion, these findings suggest mincle as a novel therapeutic target that can be used to lower the levels of TNF after CNS injury.
Published Version
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