Chemokine signaling mediated monocyte infiltration affects anxiety-like behavior following blast injury

Madhuvika Murugan, Arunreddy Ravula, Ajay Gandhi, Geetasravya Vegunta, Sushni Mukkamalla, Waleed Mujib, Namas Chandra

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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 CCR2RFP/+: CX3CR1GFP/+ 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-1β 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-1β 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.

Original languageEnglish (US)
Pages (from-to)340-352
Number of pages13
JournalBrain, Behavior, and Immunity
Volume88
DOIs
StatePublished - Aug 2020

All Science Journal Classification (ASJC) codes

  • Immunology
  • Endocrine and Autonomic Systems
  • Behavioral Neuroscience

Keywords

  • Blast
  • Brain injury
  • CCL2-CCR2 signaling
  • Chemokine
  • Microglia
  • Monocyte infiltration

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