Munch Tina Nørgaard, Hedley Paula L, Nielsen Kim Gjerum, Christiansen Michael, Jurisch-Yaksi Nathalie
Department of Neurosurgery, Copenhagen University Hospital, Copenhagen, Denmark.
Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark.
J Mol Neurosci. 2025 Sep 13;75(3):115. doi: 10.1007/s12031-025-02405-9.
Hydrocephalus is a condition defined by excessive cerebrospinal fluid (CSF) relative to the brain volume. Congenital and infantile forms of hydrocephalus are both genetically and physiologically heterogenous. Among the candidate genes implicated in hydrocephalus, many are associated with cilia, a subcellular structure involved in CSF circulation and neurodevelopment. First, we provide an overview of 129 genes associated with human hydrocephalus and currently reported in the literature, categorized according to their possible involvement in ciliary structure, ciliary function, or cilia-mediated processes/signalling pathways. Intriguingly, there are large differences in the prevalence and manifestations of cilia-related hydrocephalus in humans as compared to rodents. Second, we address these differences by revisiting human and animal studies to outline potential cilia-related mechanisms and molecular signalling pathways contributing to hydrocephalus. We propose that our rapidly expanding understanding of cilia's role in CSF circulation and brain development will support a more precise characterization of hydrocephalus subtypes, ultimately guiding the development of more personalized treatment strategies.
脑积水是一种相对于脑容量而言脑脊液（CSF）过多所定义的病症。先天性和婴儿型脑积水在遗传和生理方面均具有异质性。在与脑积水相关的候选基因中，许多基因与纤毛有关，纤毛是一种参与脑脊液循环和神经发育的亚细胞结构。首先，我们概述了129个与人类脑积水相关且目前在文献中报道的基因，这些基因根据其可能参与的纤毛结构、纤毛功能或纤毛介导的过程/信号通路进行分类。有趣的是，与啮齿动物相比，人类中与纤毛相关的脑积水在患病率和表现方面存在很大差异。其次，我们通过回顾人类和动物研究来探讨这些差异，以概述导致脑积水的潜在纤毛相关机制和分子信号通路。我们认为，我们对纤毛在脑脊液循环和脑发育中作用的快速深入理解将有助于更精确地界定脑积水亚型，最终指导制定更个性化的治疗策略。
