Abstract
Both brain native inflammatory cells and infiltrated peripheral white blood cells (WBCs) are primary participants in the brain inflammatory damage post-TBI. Metabotropic glutamate receptor 5 (mGluR5) has been reported to regulate microglias and astrocytes to affect inflammation after TBI, but its effect on modulating infiltrated peripheral WBCs remains unclear. In a mouse moderate TBI model, we found that mGluR5 knockout (KO) significantly reduced neutrophil infiltration and inflammatory cytokine expression in the brain at 24 hours post TBI, which was accompanied by improved neurological dysfunction. Further investigation indicated that mGluR5 KO reduced the permeability of blood-brain barrier (BBB), the entrance for neutrophils to enter brain, and markedly decreased the mRNA levels of neutrophil-associated chemokines in brain tissue, including CXCL1, CXCL2, CCL2, CCL4 and CCL5. Using brain microvascular endothelial cells (BMECs), neutrophils and a BBB model in vitro, we confirmed the inhibitory effect of mGluR5 deficiency on neutrophil infiltration and demonstrated that blockade of protein kinase C (PKC) signaling was involved in it. These results provide insight into the role of mGluR5 in the regulation of inflammation in the acute phase of TBI, which may provide novel clues for TBI therapy.
Highlights
Traumatic brain injury (TBI) is a common and often life-threatening clinical condition
In a mouse CCI-induced moderate TBI model, we evaluated the differences between eight-to-ten-weekold WT and Metabotropic glutamate receptor 5 (mGluR5) KO mice with respect to behavioral recovery
Less apoptotic cells in brain sections of mGluR5 KO mice were observed at 24 h post-TBI when compared to that of WT mice (Fig. 1D). These results demonstrate that neurological dysfunction was less severe in the mGluR5 KO mice in the acute phase of TBI
Summary
Traumatic brain injury (TBI) is a common and often life-threatening clinical condition. Movsesyan et al found that the inactivation of mGluR5 alleviates neuronal injury in vitro[13] and suppresses astrocytes that release proinflammatory cytokines or chemokines[14] These studies provide important clues for understanding the mGluR5 function in regulating brain native cells that participate in inflammation and brain damage after TBI. It is not clear about the role of mGluR5 in the modulation of peripheral immune cells (such as neutrophils) during the course. In the present study, we focused on the effect of mGluR5 on peripheral neutrophil infiltration and associated brain damages in the acute phase of TBI, which is expected to provide insight regarding mGluR5 in TBI and novel clues for TBI therapy
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