Sustained peripheral immune hyper-reactivity (SPIHR): an enduring biomarker of altered inflammatory responses in adult rats after perinatal brain injury.
Sustained peripheral immune hyper-reactivity (SPIHR): an enduring biomarker of altered inflammatory responses in adult rats after perinatal brain injury.
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持续性外周免疫高反应性（SPIHR）：围产期脑损伤后成年大鼠炎症反应改变的持久生物标志物。
DOI：
10.1186/s12974-021-02291-z
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发表时间：
2021-10-19
影响因子：
9.3
通讯作者：
Jantzie LL
中科院分区：
文献类型：
--
作者：
Kitase Y;Chin EM;Ramachandra S;Burkhardt C;Madurai NK;Lenz C;Hoon AH Jr;Robinson S;Jantzie LL
绒毛膜羊膜炎（CHORIO）是早产的主要危险因素，是早产儿胎盘中最常见的病理异常。CHORIO对母体-胎盘-胎儿轴有多种影响，包括严重的炎症。累积起来，这些变化会引发正在发育的免疫系统和中枢神经系统的损伤，从而增加了以后生活中慢性后遗症的易感性。尽管有这方面的报道以及脑瘫儿童神经免疫改变的报道，但CHORIO继发的外周免疫和神经炎症改变的程度和慢性性尚未得到充分表征。我们在一个已建立并可转化的CHORIO继发围产期脑损伤（PBI）模型中检测了外周免疫高反应性的持久性和时间过程。妊娠的Sprague-Dawley大鼠在胚胎第18天（E18，早产当量）进行剖腹手术。子宫动脉闭塞60分钟，然后羊膜内注射脂多糖（LPS）。青年人（出生后60天）和中年人（出生后120天）采集血清和外周血单个核细胞（PBMCs）。采用多重电化学发光免疫法检测血清和外周血单核细胞分泌组趋化因子和细胞因子。采用多参数流式细胞术检测免疫细胞群。血清白细胞介素-1β (IL-1β)、IL-5、IL-6、C-X-C基序趋化因子配体1 （CXCL1）、肿瘤坏死因子-α (TNF-α)和C-C基序趋化因子配体2/单核细胞趋化蛋白-1 （CCL2/MCP-1）水平在P60时显著高于对照组。值得注意的是，CHORIO pbmc被启动。具体来说，它们在基线和体外刺激时都反应过度，分泌更多的炎症介质。在CHORIO动物中，当血清细胞因子水平被P120正常化时，PBMCs仍处于启动状态，并且在多个T细胞群中具有强烈的促炎分泌组和持续变化的高反应性。数据表明，子宫内的炎症性损伤会导致神经免疫系统的变化，这种变化会持续到成年期，从而使大脑和免疫系统在整个生命周期中都容易受到损伤。这种独特的分子和细胞免疫特征，包括持续的外周免疫高反应性（SPIHR）和免疫细胞启动，可能是子宫内损伤后炎症反应改变的可行生物标志物，并促进了我们对导致围产期脑损伤和后来的神经发育障碍（包括脑瘫）的神经炎症级联反应的理解。
Chorioamnionitis (CHORIO) is a principal risk factor for preterm birth and is the most common pathological abnormality found in the placentae of preterm infants. CHORIO has a multitude of effects on the maternal–placental–fetal axis including profound inflammation. Cumulatively, these changes trigger injury in the developing immune and central nervous systems, thereby increasing susceptibility to chronic sequelae later in life. Despite this and reports of neural–immune changes in children with cerebral palsy, the extent and chronicity of the peripheral immune and neuroinflammatory changes secondary to CHORIO has not been fully characterized. We examined the persistence and time course of peripheral immune hyper-reactivity in an established and translational model of perinatal brain injury (PBI) secondary to CHORIO. Pregnant Sprague–Dawley rats underwent laparotomy on embryonic day 18 (E18, preterm equivalent). Uterine arteries were occluded for 60 min, followed by intra-amniotic injection of lipopolysaccharide (LPS). Serum and peripheral blood mononuclear cells (PBMCs) were collected at young adult (postnatal day P60) and middle-aged equivalents (P120). Serum and PBMCs secretome chemokines and cytokines were assayed using multiplex electrochemiluminescent immunoassay. Multiparameter flow cytometry was performed to interrogate immune cell populations. Serum levels of interleukin-1β (IL-1β), IL-5, IL-6, C–X–C Motif Chemokine Ligand 1 (CXCL1), tumor necrosis factor-α (TNF-α), and C–C motif chemokine ligand 2/monocyte chemoattractant protein-1 (CCL2/MCP-1) were significantly higher in CHORIO animals compared to sham controls at P60. Notably, CHORIO PBMCs were primed. Specifically, they were hyper-reactive and secreted more inflammatory mediators both at baseline and when stimulated in vitro. While serum levels of cytokines normalized by P120, PBMCs remained primed, and hyper-reactive with a robust pro-inflammatory secretome concomitant with a persistent change in multiple T cell populations in CHORIO animals. The data indicate that an in utero inflammatory insult leads to neural–immune changes that persist through adulthood, thereby conferring vulnerability to brain and immune system injury throughout the lifespan. This unique molecular and cellular immune signature including sustained peripheral immune hyper-reactivity (SPIHR) and immune cell priming may be a viable biomarker of altered inflammatory responses following in utero insults and advances our understanding of the neuroinflammatory cascade that leads to perinatal brain injury and later neurodevelopmental disorders, including cerebral palsy.
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影响因子：
5.7
作者：
Batalle D;Hughes EJ;Zhang H;Tournier JD;Tusor N;Aljabar P;Wali L;Alexander DC;Hajnal JV;Nosarti C;Edwards AD;Counsell SJ
通讯作者：
Counsell SJ
影响因子：
9.2
作者：
Erta M;Quintana A;Hidalgo J
通讯作者：
Hidalgo J
影响因子：
20.3
作者：
Biswas, P;Delfanti, F;Poli, G
通讯作者：
Poli, G
影响因子：
64.8
作者：
Baggiolini, M
通讯作者：
Baggiolini, M
DOI：
10.1073/pnas.91.9.3652
发表时间：
1994-04-26
影响因子：
11.1
作者：
CARR, MW;ROTH, SJ;SPRINGER, TA
通讯作者：
SPRINGER, TA