背景:围产期缺氧会触发神经元释放细胞因子和趋化因子,星形胶质细胞和小胶质细胞。响应缺氧缺血静息/分支小胶质细胞增殖并经历激活,产生促炎分子。脑损伤的扩展似乎与缺氧的严重程度以及促炎和抗炎反应之间的平衡有关,可以通过神经影像学进行探索。
目的:这项初步研究的目的是探索血浆炎性细胞因子/趋化因子水平与磁共振成像(MRI)可检测到的严重脑损伤之间的可能关系,在住院期间进行。
方法:在10例接受治疗性低温(TH)的缺氧缺血性脑病(HIE)新生儿中,分为案例和控制,根据核磁共振结果,我们测量并比较了血浆CCL2/MCP-1,CXCL8,GFAP,IFNy,IL-10,IL-18,IL-6,CCL3,ENOLASE2,GM-CSF,IL-1b,IL-12p70,IL-33,TNFα,在TH期间的四个不同时间点收集(生命的24、25-48、49-72小时,和出生后7-10天)。5名入选婴儿进行了病理性脑MRI检查(病例),5名进行了正常的MRI检查(对照)。通过磁性Luminex测定法测量细胞因子。MRI图像根据Barkovich评分进行分类。
结果:在时间T1,所有细胞因子和分子的平均水平在两组中没有显著差异。比较按采集日期配对的样本,在TH期间,病例和对照组之间的最大差异是在T2和T3时间。在T4时,水平趋于再次接近(除了IL-6、IL10和IL18)。MRI较差的婴儿显示血浆GFAP水平高于MRI正常的婴儿,而他们的IL-18较低。CCL3MIP1alpha的平均水平,GMCSF,两组IL1BETA在整个观察期间重叠。
结论:在少数脑部MRI较差的婴儿中,我们发现,与MRI正常的婴儿相比,T4时GFAP和IL-10水平较高,IL-18水平较低。被认为是脑损伤的早期生物标志物和不良结局的预测因子,分别。最伟大的,虽然不重要,在TH期间,在T2和T3时间点的病例和对照中发现分子水平之间的差异。
Perinatal hypoxia triggers the release of cytokines and chemokines by neurons, astrocytes and microglia. In response to hypoxia-ischemia resting/ramified microglia proliferate and undergo activation, producing proinflammatory molecules. The brain damage extension seems to be related to both the severity of hypoxia and the balance between pro and anti-inflammatory response and can be explored with neuroimaging.
The aim of this preliminary study was to explore possible relationships between plasma levels of inflammatory cytokines/chemokines and the severe brain damage detectable by Magnetic Resonance Imaging (MRI), performed during the hospitalization.
In 10 full terms neonates with hypoxic ischemic encephalopathy (HIE) undergoing therapeutic hypothermia (TH), divided into cases and controls, according to MRI results, we measured and compared the plasma levels of CCL2/MCP-1, CXCL8, GFAP, IFN y, IL-10, IL-18, IL-6, CCL3, ENOLASE2, GM-CSF, IL-1b, IL-12p70, IL-33, TNFα, collected at four different time points during TH (24, 25-48, 49-72 h of life, and 7-10 days from birth). Five of enrolled babies had pathological brain MRI (cases) and 5 had a normal MRI examination (controls). Cytokines were measured by Magnetic Luminex Assay. MRI images were classified according to Barkovich\'s score.
Mean levels of all cytokines and molecules at time T1 were not significantly different in the two groups. Comparing samples paired by day of collection, the greatest differences between cases and controls were found at times T2 and T3, during TH. At T4, levels tended to get closer again (except for IL-6, IL10 and IL18). Infants with worse MRI showed higher plasmatic GFAP levels than those with normal MRI, while their IL-18 was lower. The mean levels of CCL3MIP1alpha, GMCSF, IL1BETA overlapped throughout the observation period in both groups.
In a small number of infants with worse brain MRI, we found higher levels of GFAP and of IL-10 at T4 and a trend toward low IL-18 levels than in infants with normal MRI, considered early biomarker of brain damage and a predictor of adverse outcome, respectively. The greatest, although not significant, difference between the levels of molecules was found in cases and controls at time points T2 and T3, during TH.