The Cerebrospinal Fluid Inflammatory Response to Preterm Birth.
The Cerebrospinal Fluid Inflammatory Response to Preterm Birth.
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DOI：
10.3389/fphys.2018.01299
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发表时间：
2018
影响因子：
4
通讯作者：
Miron V
中科院分区：
文献类型：
--
作者：
Boardman JP;Ireland G;Sullivan G;Pataky R;Fleiss B;Gressens P;Miron V
背景：早产是围产期白质损伤的主要危险因素，可导致整个生命过程中的运动和神经精神障碍。对治疗方法的临床需求尚未得到满足。白质损伤与大脑炎症反应的改变有关，主要由小胶质细胞引起，随后是髓鞘化降低。然而，小胶质细胞在损伤反应中可以释放损伤因子和营养因子，而早产儿中枢神经系统（CNS）中这些因子的综合评估尚未开展。方法：使用定制抗体阵列来评估早产儿脑脊液（CSF）中50种炎症和髓鞘相关蛋白的相对水平，并与足月对照组进行比较。结果：BDNF、BTC、C5a、FasL、Follistatin、IL-1β、IL-2、IL-4、IL-9、IL-17A、MIP-1α、MMP8、SPP1、TGFβ、TNFβ 15种蛋白组间差异有统计学意义（p < 0.05）。为了研究这些蛋白在损伤后的时间调控，我们挖掘了从发育性白质损伤小鼠模型中分离的小胶质细胞的基因表达数据集。实验模型中的小胶质细胞显示编码这些蛋白质的基因的动态时间表达，具有初始和持续的促炎反应，随后是延迟的抗炎反应，以及预测抑制健康髓鞘形成的基因的持续表达。结论：与足月对照组相比，早产儿脑脊液显示出明显的神经炎症特征，提示存在复杂的神经环境，同时存在损伤和修复信号。我们认为，围产期损伤后早期发生的促炎反应可能会阻止髓鞘抑制基因的表达，从而支持健康的白质发育。
Background: Preterm birth is the leading risk factor for perinatal white matter injury, which can lead to motor and neuropsychiatric impairment across the life course. There is an unmet clinical need for therapeutics. White matter injury is associated with an altered inflammatory response in the brain, primarily led by microglia, and subsequent hypomyelination. However, microglia can release both damaging and trophic factors in response to injury, and a comprehensive assessment of these factors in the preterm central nervous system (CNS) has not been carried out. Method: A custom antibody array was used to assess relative levels of 50 inflammation- and myelination-associated proteins in the cerebrospinal fluid (CSF) of preterm infants in comparison to term controls. Results: Fifteen proteins differed between the groups: BDNF, BTC, C5a, FasL, Follistatin, IL-1β, IL-2, IL-4, IL-9, IL-17A, MIP-1α, MMP8, SPP1, TGFβ, and TNFβ (p < 0.05). To investigate the temporal regulation of these proteins after injury, we mined a gene expression dataset of microglia isolated from a mouse model of developmental white matter injury. Microglia in the experimental model showed dynamic temporal expression of genes encoding these proteins, with an initial and sustained pro-inflammatory response followed by a delayed anti-inflammatory response, and a continuous expression of genes predicted to inhibit healthy myelination. Conclusion: Preterm CSF shows a distinct neuroinflammatory profile compared to term controls, suggestive of a complex neural environment with concurrent damaging and reparative signals. We propose that limitation of pro-inflammatory responses, which occur early after perinatal insult, may prevent expression of myelination-suppressive genes and support healthy white matter development.
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影响因子：
5.1
作者：
Carlo, Waldemar A.;McDonald, Scott A.;Tyson, Jon E.;Stoll, Barbara J.;Ehrenkranz, Richard A.;Shankaran, Seetha;Goldberg, Ronald N.;Das, Abhik;Schendel, Diana;Thorsen, Poul;Skogstrand, Kristin;Hougaard, David M.;Oh, William;Laptook, Abbot R.;Duara, Shahnaz;Fanaroff, Avroy A.;Donovan, Edward F.;Korones, Sheldon B.;Stevenson, David K.;Papile, Lu-Ann;Finer, Neil N.;O'Shea, T. Michael;Poindexter, Brenda B.;Wright, Linda L.;Ambalavanan, Namasivayam;Higgins, Rosemary D.
通讯作者：
Higgins, Rosemary D.
影响因子：
3.6
作者：
Ding X;Cao F;Cui L;Ciric B;Zhang GX;Rostami A
通讯作者：
Rostami A
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
早产过早破裂后神经系统残疾的炎症预测因子。
影响因子：
9.8
作者：
Armstrong-Wells, Jennifer;Donnelly, Meghan;Post, Miriam D.;Manco-Johnson, Marilyn J.;Winn, Virginia D.;Sebire, Guillaume
通讯作者：
Sebire, Guillaume
影响因子：
3.6
作者：
Bartha, AI;Foster-Barber, A;Ferriero, DM
通讯作者：
Ferriero, DM