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Colony-Stimulating Factor-1 Receptor Inhibition Transiently Attenuated the Peripheral Immune Response to Experimental Traumatic Brain Injury.
Giordano, Katherine R; Saber, Maha; Green, Tabitha R F; Rojas-Valencia, Luisa M; Ortiz, J Bryce; Murphy, Sean M; Lifshitz, Jonathan; Rowe, Rachel K.
Afiliação
  • Giordano KR; BARROW Neurological Institute at Phoenix Children's Hospital, Phoenix, Arizona, USA.
  • Saber M; Department of Child Health, University of Arizona College of Medicine-Phoenix, Phoenix, Arizona, USA.
  • Green TRF; Phoenix Veteran Affairs Health Care System, Phoenix, Arizona, USA.
  • Rojas-Valencia LM; BARROW Neurological Institute at Phoenix Children's Hospital, Phoenix, Arizona, USA.
  • Ortiz JB; Department of Child Health, University of Arizona College of Medicine-Phoenix, Phoenix, Arizona, USA.
  • Murphy SM; Department of Child Health, University of Arizona College of Medicine-Phoenix, Phoenix, Arizona, USA.
  • Lifshitz J; Department of Integrative Physiology, University of Colorado Boulder, Boulder, Colorado, USA.
  • Rowe RK; BARROW Neurological Institute at Phoenix Children's Hospital, Phoenix, Arizona, USA.
Neurotrauma Rep ; 4(1): 284-296, 2023.
Article em En | MEDLINE | ID: mdl-37139183
ABSTRACT
To investigate microglial mechanisms in central and peripheral inflammation after experimental traumatic brain injury (TBI), we inhibited the colony-stimulating factor-1 receptor (CSF-1R) with PLX5622 (PLX). We hypothesized that microglia depletion would attenuate central inflammation acutely with no effect on peripheral inflammation. After randomization, male mice (n = 105) were fed PLX or control diets (21 days) and then received midline fluid percussion injury or sham injury. Brain and blood were collected at 1, 3, or 7 days post-injury (DPI). Immune cell populations were quantified in the brain and blood by flow cytometry. Cytokines (interleukin [IL]-6, IL-1ß, tumor necrosis factor-α, interferon-γ, IL-17A, and IL-10) were quantified in the blood using a multi-plex enzyme-linked immunosorbent assay. Data were analyzed using Bayesian multi-variate, multi-level models. PLX depleted microglia at all time points and reduced neutrophils in the brain at 7 DPI. PLX also depleted CD115+ monocytes, reduced myeloid cells, neutrophils, and Ly6Clow monocytes in blood, and elevated IL-6. TBI induced a central and peripheral immune response. TBI elevated leukocytes, microglia, and macrophages in the brain and elevated peripheral myeloid cells, neutrophils, Ly6Cint monocytes, and IL-1ß in the blood. TBI lowered peripheral CD115+ and Ly6Clow monocytes in the blood. TBI PLX mice had fewer leukocytes and microglia in the brain at 1 DPI, with elevated neutrophils at 7 DPI compared to TBI mice on a control diet. TBI PLX mice also had fewer peripheral myeloid cells, CD115+, and Ly6Clow monocytes in the blood at 3 DPI, but elevated Ly6Chigh, Ly6Cint, and CD115+ monocyte populations at 7 DPI, compared to TBI mice on a control diet. TBI PLX mice had elevated proinflammatory cytokines and lower anti-inflammatory cytokines in the blood at 7 DPI compared to TBI mice on a control diet. CSF-1R inhibition reduced the immune response to TBI at 1 and 3 DPI, but elevated peripheral inflammation at 7 DPI.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Clinical_trials / Prognostic_studies Idioma: En Revista: Neurotrauma Rep Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Clinical_trials / Prognostic_studies Idioma: En Revista: Neurotrauma Rep Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos