| First Author | Murugan M | Year | 2020 |
| Journal | Brain Behav Immun | Volume | 88 |
| Pages | 340-352 | PubMed ID | 32240765 |
| Mgi Jnum | J:338003 | Mgi Id | MGI:6819563 |
| Doi | 10.1016/j.bbi.2020.03.029 | Citation | Murugan M, et al. (2020) Chemokine signaling mediated monocyte infiltration affects anxiety-like behavior following blast injury. Brain Behav Immun 88:340-352 |
| abstractText | The activation of resident microglia and infiltrated monocytes are known potent mediators of chronic neuroinflammation following traumatic brain injury (TBI). In this study, we use a mouse model of blast-induced TBI (bTBI) to investigate whether microglia and monocytes contribute to the neuroinflammatory and behavioral consequences of bTBI. Eight-ten week old mice were subject to moderate TBI (180 kPa) in a shock tube. Using double transgenic CCR2(RFP/+:) CX3CR1(GFP/+) mice, we were able to note that in addition to resident Cx3CR1+ microglia, infiltrating CCR2+ monocytes also contributed to the expanding macrophage population that was observed after bTBI. The microglia activation and monocyte infiltration occurred as early as 4 h and lasted up to 30d after blast exposure, suggesting chronic inflammation. The infiltration of monocytes may be partly mediated by chemokine CCL2-CCR2 signaling axis and compromised blood brain barrier permeability. Hence, bTBI-induced infiltration of monocytes and production of IL-1beta were prevented in mice lacking CCR2 (CCR2 KO). Finally, this study showed that interference of monocyte infiltration using CCR2 KO, ameliorated the chronic effects of bTBI such as anxiety-like behavior and short-term memory decline. Taken together, these data suggest that bTBI leads to activation of both resident microglia and infiltrated monocytes. The infiltration of monocytes was partly mediated by CCL2-CCR2 signaling, which in turn contributes to increased production of IL-1beta leading to behavioral deficits after bTBI. Furthermore, bTBI induced behavioral outcomes were reduced by targeting CCL2-CCR2 signaling, highlighting the significance of this signaling axis in bTBI pathology. |
