Department of Women´s and Children´s Health, Karolinska Institutet, Stockholm, Sweden.
Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.
Acta Paediatr. 2022 May;111(5):961-970. doi: 10.1111/apa.16277. Epub 2022 Feb 17.
Perinatal asphyxia, resulting in hypoxic-ischaemic encephalopathy (HIE), has been associated with high mortality rates and severe lifelong neurodevelopmental disabilities. Our aim was to study the association between the proteomic profile in cerebrospinal fluid (CSF) and the degree of HIE and long-term outcomes.
We prospectively enrolled 18-term born infants with HIE and 10-term born controls between 2000 and 2004 from the Karolinska University Hospital. An antibody suspension bead array and FlexMap3D analysis was used to characterise 178 unique brain-derived and inflammation associated proteins in their CSF.
Increased CSF concentrations of several brain-specific proteins were observed in the proteome of HIE patients compared with the controls. An upregulation of neuroinflammatory pathways was also noted and this was confirmed by pathway analysis. Principal component analysis revealed a gradient from favourable to unfavourable HIE grades and outcomes. The proteins that provided strong predictors were structural proteins, including myelin basic protein and alpha-II spectrin. The functional proteins included energy-related proteins like neuron-specific enolase and synaptic regulatory proteins. Increased CSF levels of 51 proteins correlated with adverse outcomes in infants with HIE.
Brain-specific proteins and neuroinflammatory mediators in CSF may predict HIE degrees and outcomes after perinatal asphyxia.
围产期窒息导致的缺氧缺血性脑病（HIE）与高死亡率和严重的终身神经发育障碍有关。我们的目的是研究脑脊液（CSF）中的蛋白质组谱与 HIE 程度和长期结局之间的关联。
我们前瞻性地招募了 18 名胎龄足月出生的 HIE 患儿和 10 名胎龄足月出生的对照组婴儿，他们均于 2000 年至 2004 年在卡罗林斯卡大学医院就诊。采用抗体悬浮珠阵列和 FlexMap3D 分析技术，对其 CSF 中的 178 种独特的脑源性和炎症相关蛋白进行特征分析。
与对照组相比，HIE 患者的 CSF 中几种脑特异性蛋白的浓度升高。还观察到神经炎症途径的上调，这通过途径分析得到了证实。主成分分析显示，从有利的 HIE 分级和结局到不利的分级和结局存在梯度。提供强预测指标的蛋白质是结构蛋白，包括髓鞘碱性蛋白和α-II spectrin。功能性蛋白质包括神经元特异性烯醇化酶和突触调节蛋白等与能量相关的蛋白质。51 种 CSF 水平升高的蛋白质与 HIE 婴儿的不良结局相关。
CSF 中的脑特异性蛋白和神经炎症介质可能预测围产期窒息后 HIE 的严重程度和结局。
