Hale Andrew T, Zhou Blake, Rajan Arjun, Duy Phan Q, Goolam Mubeen, Alper Seth L, Lehtinen Maria K, Lancaster Madeline A, Fame Ryann M, Kahle Kristopher T
Department of Neurosurgery, University of Alabama at Birmingham, Birmingham, AL 35233, USA.
Department of Human Biology and Neuroscience Institute, University of Cape Town, Cape Town 7925, South Africa.
Sci Transl Med. 2025 Jun 4;17(801):eadq1810. doi: 10.1126/scitranslmed.adq1810.
Hydrocephalus (HC) is a failure of brain and cerebrospinal fluid (CSF) homeostasis often associated with dilation of the CSF-filled ventricles (ventriculomegaly). Hallmarks of HC include aberrant CSF dynamics, neural stem cell dysfunction resulting in impaired neurogenesis and corticogenesis, biomechanical instability at the brain-CSF interface, and disrupted synaptogenesis and neural circuitry. Pleiotropic mechanisms, including genetic and environmental insults to the brain, contribute to neurodevelopmental comorbidities. Hypothesis generation from genome-wide, single-cell multi-omic analyses coupled to experimental validation using induced pluripotent stem cell-derived cerebral organoids will refine molecular classification of HC subtypes and may lead to precision-based surgical and pharmacologic treatments.
脑积水（HC）是脑和脑脊液（CSF）稳态失衡的一种疾病，常伴有充满脑脊液的脑室扩张（脑室扩大）。脑积水的特征包括脑脊液动力学异常、神经干细胞功能障碍导致神经发生和皮质发生受损、脑-脑脊液界面的生物力学不稳定，以及突触发生和神经回路破坏。包括对大脑的遗传和环境损伤在内的多效性机制会导致神经发育合并症。通过全基因组、单细胞多组学分析生成假设，并结合使用诱导多能干细胞衍生的脑类器官进行实验验证，将完善脑积水亚型的分子分类，并可能带来基于精准医学的手术和药物治疗。
