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

Authors

Madhuvika Murugan, Newark College of Engineering
Arunreddy Ravula, Newark College of Engineering
Ajay Gandhi, Newark College of Engineering
Geetasravya Vegunta, Newark College of Engineering
Sushni Mukkamalla, Newark College of Engineering
Waleed Mujib, Newark College of Engineering
Namas Chandra, Newark College of Engineering

Document Type

Article

Publication Date

8-1-2020

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 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-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.

Identifier

85082848942 (Scopus)

Publication Title

Brain Behavior and Immunity

External Full Text Location

https://doi.org/10.1016/j.bbi.2020.03.029

e-ISSN

10902139

ISSN

08891591

PubMed ID

32240765

First Page

340

Last Page

352

Volume

88

Grant

W81XWH-15-1-0303

Fund Ref

Medical Research and Materiel Command

Recommended Citation

Murugan, Madhuvika; Ravula, Arunreddy; Gandhi, Ajay; Vegunta, Geetasravya; Mukkamalla, Sushni; Mujib, Waleed; and Chandra, Namas, "Chemokine signaling mediated monocyte infiltration affects anxiety-like behavior following blast injury" (2020). Faculty Publications. 5101.
https://digitalcommons.njit.edu/fac_pubs/5101