Peripheral and central markers of inflammation after experimental brain injury in mice with depleted or intact microglia

DOI:10.34945/F5901R

DATASET CITATION

Rowe R. K., Giordano K. R., Saber M., Green T. R.F.., Rojas-Valencia L. M., Ortiz J., Murphy S. M., Lifshitz J. (2022) Peripheral and central markers of inflammation after experimental brain injury in mice with depleted or intact microglia. ODC-TBI:769 http://doi.org/10.34945/F5901R

ABSTRACT

STUDY PURPOSE: Inflammation is a hallmark of traumatic brain injury (TBI) pathophysiology that contributes to both brain damage and its repair. To investigate microglial mechanisms in central and peripheral inflammation following TBI, we inhibited the colony stimulating factor-1 receptor (CSF-1R), critical for microglial survival, with PLX5622 (PLX). We hypothesized that microglia depletion would attenuate central inflammation acutely.

DATA COLLECTED: After randomization, adult male C57BL/6J mice (n = 105) were fed PLX5622 (1200 mg/kg, Plexxikon) or control (AIN-76A rodent chow) diets (21 days) and then received midline fluid percussion injury (mFPI) or sham injury. Blood and brain were collected at 1, 3, or 7 days post-injury (DPI). Immune cell populations (leukocytes, myeloid cells, microglia, monocytes, macrophages, neutrophils) were quantified in the brain and blood by flow cytometry. Pro-inflammatory cytokines (interleukin [IL]-6, IL-1?, tumor necrosis factor [TNF]-?, IFN [interferon]-?) and anti-inflammatory cytokines (IL-10, IL-17A) were quantified in the blood using multiplex ELISA.

CONCLUSIONS: CSF-1R inhibition blunted the immune response to TBI at 1 and 3 day post-injury but elevated peripheral inflammation at 7 days post-injury. CSF-1R inhibition may be a plausible mechanism to target both central and peripheral immune cells and change the long-term inflammatory response to TBI. However, administration of PLX as a research tool to target microglia-mediated inflammation should be used with caution, as we also observed several off-target inflammatory effects of CSF-1R inhibition, independent of brain injury. Specifically, CD115+ peripheral monocytes were depleted.

KEYWORDS

microglia; Inflammation; CSF-1 receptor; immune cell activation; Cytokine; Traumatic brain injury

PROVENANCE / ORIGINATING PUBLICATIONS

RELEVANT LINKS

NOTES

DATASET INFO

Contact: Rowe Rachel (rachel.rowe@colorado.edu)

Lab: Rachel Rowe

ODC-TBI Accession:769

Records in Dataset: 105

Fields per Record: 39

Last updated: 2023-04-12

Date published: 2023-04-12

Downloads: 17

Files: 2

LICENSE

Creative Commons Attribution License (CC-BY 4.0)

FUNDING AND ACKNOWLEDGEMENTS

NINDS F31NS113408

CONTRIBUTORS

Rowe, Rachel K. [ORCID:0000-0002-9034-3159]

Department of Integrative Physiology, University of Colorado – Boulder, Boulder, CO, USA

Giordano, Katherine R.

BARROW Neurological Institute at Phoenix Children’s Hospital, Department of Child Health, University of Arizona College of Medicine – Phoenix, Phoenix, AZ, USA, Phoenix, AZ, USA, Phoenix Veteran Affairs Health Care System, Phoenix, AZ, USA

Saber, Maha

BARROW Neurological Institute at Phoenix Children’s Hospital, Phoenix, AZ, USA, Department of Child Health, University of Arizona College of Medicine – Phoenix, Phoenix, AZ, USA

Green, Tabitha R.F..

BARROW Neurological Institute at Phoenix Children’s Hospital, Phoenix, AZ, USA, Department of Child Health, University of Arizona College of Medicine – Phoenix, Phoenix, AZ, USA

Rojas-Valencia, Luisa M.

BARROW Neurological Institute at Phoenix Children’s Hospital, Department of Child Health, University of Arizona College of Medicine – Phoenix, Phoenix, AZ, USA, Phoenix, AZ, USA, Phoenix Veteran Affairs Health Care System, Phoenix, AZ, USA

Ortiz, J. Bryce

BARROW Neurological Institute at Phoenix Children’s Hospital, Department of Child Health, University of Arizona College of Medicine – Phoenix, Phoenix, AZ, USA, Phoenix, AZ, USA, Phoenix Veteran Affairs Health Care System, Phoenix, AZ, USA

Murphy, Sean M.

Department of Child Health, University of Arizona College of Medicine – Phoenix, Phoenix, AZ, USA

Lifshitz, Jonathan

BARROW Neurological Institute at Phoenix Children’s Hospital, Department of Child Health, University of Arizona College of Medicine – Phoenix, Phoenix, AZ, USA, Phoenix, AZ, USA, Phoenix Veteran Affairs Health Care System, Phoenix, AZ, USA