The aetiology of congenital hydrocephalus (cHC) has yet to be resolved. cHC manifests late in rodent gestation, and by 18–22 weeks in human fetuses, coinciding with the start of the major phase of cerebral cortex development. Previously we found that cerebrospinal fluid (CSF) accumulation is associated with compositional changes, folate metabolic impairment and consequential arrest in cortical development. Here, we report a proteomics study on hydrocephalic and normal rat CSF using LC-MSMS and a metabolic pathway analysis to determine the major changes in metabolic and signalling pathways. Non-targeted analysis revealed a proteome transformation across embryonic days 17–20, with the largest changes between day 19 and 20. This provides evidence for a physiological shift in CSF composition and identifies some of the molecular mechanisms unleashed during the onset of cHC. Top molecular regulators that may control the shift in the CSF metabolic signature are also predicted, with potential key biomarkers proposed for early detection of these changes that might be used to develop targeted early therapies for this condition. This study confirms previous findings of a folate metabolic imbalance as well as providing more in depth metabolic analysis and understanding of cHC CSF.

先天性脑积水（cHC）的病因尚未解决。 cHC 出现在啮齿类动物妊娠晚期，而在人类胎儿中则出现在 18-22 周，此时恰逢大脑皮层发育主要阶段的开始。之前我们发现脑脊液（CSF）积聚与成分变化、叶酸代谢障碍以及随之而来的皮质发育停滞有关。在这里，我们报告了一项使用 LC-MSMS 和代谢途径分析对脑积水和正常大鼠 CSF 进行的蛋白质组学研究，以确定代谢和信号传导途径的主要变化。非靶向分析揭示了胚胎第 17 天至第 20 天的蛋白质组转变，其中第 19 天至第 20 天的变化最大。这为脑脊液组成的生理变化提供了证据，并确定了 cHC 发作期间释放的一些分子机制。还预测了可能控制脑脊液代谢特征转变的顶级分子调节剂，并提出了用于早期检测这些变化的潜在关键生物标志物，这些变化可用于开发针对这种情况的有针对性的早期疗法。这项研究证实了之前关于叶酸代谢失衡的发现，并提供了对 cHC CSF 更深入的代谢分析和理解。