Colony-Stimulating Factor-1 Receptor Inhibition Transiently Attenuated the Peripheral Immune Response to Experimental Traumatic Brain Injury.
Colony-Stimulating Factor-1 Receptor Inhibition Transiently Attenuated the Peripheral Immune Response to Experimental Traumatic Brain Injury.
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DOI：
10.1089/neur.2022.0092
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发表时间：
2023
影响因子：
2.4
通讯作者：
Rowe, Rachel K. K.
中科院分区：
文献类型：
--
作者：
Giordano, Katherine R. R.;Saber, Maha;Green, Tabitha R. F.;Rojas-Valencia, Luisa M. M.;Ortiz, J. Bryce;Murphy, Sean M. M.;Lifshitz, Jonathan;Rowe, Rachel K. K.
为了探讨实验性创伤性脑损伤(TBI)后中枢和外周炎症的小胶质细胞机制，我们用PLX5622(PLX)抑制了集落刺激因子-1受体(CSF-1R)。我们假设小胶质细胞枯竭可以显著减轻中心性炎症，而对外周炎症没有影响。随机将雄性 = 小鼠(n=105)随机分为两组，分别给予PLX或对照组饲料(21d)，然后进行中线液压冲击伤或假损伤。分别于伤后1、3、7d采集脑组织和血样。用流式细胞仪对脑和血液中的免疫细胞群进行定量。细胞因子(IL-6、IL-1β、肿瘤坏死因子-α、干扰素-γ、IL-17A和IL-10)采用多重酶联免疫吸附试验进行定量。数据采用贝叶斯多变量、多水平模型进行分析。PLX在所有时间点均耗尽小胶质细胞，7DPI时脑内中性粒细胞减少。PLX还耗尽了CD115+单核细胞，减少了血液中的髓系细胞、中性粒细胞和Ly6Clow单核细胞，并升高了IL-6。TBI可诱导中枢和外周免疫应答。脑损伤后脑内白细胞、小胶质细胞和巨噬细胞增多，血液中外周髓系细胞、中性粒细胞、单核细胞和IL-1β升高。TBI可降低外周血CD115+和Ly6Clow单核细胞数。与对照组相比，TBI PLX小鼠在1DPI时脑组织中的白细胞和小胶质细胞较少，而在7DPI时中性粒细胞升高。与对照组相比，TBI PLX小鼠在3DPI时血液中外周血髓系细胞、CD115+和Ly6Clow单核细胞的数量也较少，但在7DPI时增加了Ly6Chigh、Ly6Cint和CD115+单核细胞的数量。与对照饮食的TBI小鼠相比，TBI PLX小鼠在7DPI时血液中促炎症细胞因子升高，抗炎细胞因子降低。抑制CSF-1R可降低伤后1d和3d的免疫反应，但在7d时可增加外周炎症反应。
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-1β, 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-1β 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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创伤性脑损伤后，靶向慢性和发展的神经炎症以改善长期结局：小胶质细胞模型的见解。
影响因子：
6.1
作者：
Henry RJ;Loane DJ
通讯作者：
Loane DJ
影响因子：
1.8
作者：
Figueroa-Zuniga, Jorge I.;Arellano-Valle, Reinaldo B.;Ferrari, Silvia L. P.
通讯作者：
Ferrari, Silvia L. P.
影响因子：
5.4
作者：
Brambor, T;Clark, WR;Golder, M
通讯作者：
Golder, M
影响因子：
4.7
作者：
DiSabato DJ;Quan N;Godbout JP
通讯作者：
Godbout JP
DOI：
10.1249/mss.0b013e31819fcd1b
发表时间：
2009-09-01
期刊：
MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
影响因子：
--
作者：
Hosseini, Ario H.;Lifshitz, Jonathan
通讯作者：
Lifshitz, Jonathan