Jalali Samar, Mohazeb Ali, Rezaeikalantari Nika, Fu Yang, Mohazeb Yasamin, Jiao Guanjun, Zhang Xinli
Section of Orthodontics, Division of Growth and Development, School of Dentistry, University of California, Los Angeles, Los Angeles, California, USA.
Section of Biosystems and Function, Division of Oral and Systemic Health Sciences, School of Dentistry, University of California, Los Angeles, Los Angeles, California, USA.
Orthod Craniofac Res. 2025 May 13. doi: 10.1111/ocr.12942.
Hydrocephalus, a pathological condition due to the accumulation of cerebrospinal fluid (CSF) in the brain's ventricles, has been recognised as a relatively common brain abnormality in newborns and young adults with or without craniofacial anomaly. It can cause physical, behavioural and cognitive symptoms and, in severe cases, may result in lethality. Hydrocephalus can result from various underlying conditions, and its multifactorial nature makes pinpointing a single pathophysiological aetiology challenging. Notably, the relatively high prevalence of hydrocephalus (up to 100%) in the cranial neural crest cells (CNCCs) conditional knockout mouse models of various genes using Wnt1-Cre has been reported, given the extremely low (0.01% to 0.86%) spontaneous occurrence of hydrocephalus in different strains of lab mice. Surprisingly, there were no reports on the connections of hydrocephalus with CNCCs, although the prominent role of CNCCs in normal development and pathologic conditions of craniofacial and neural tissues has been extensively studied and highly recognised. In this review, besides revealing the high prevalence of hydrocephalus (5.4%-100%), we primarily summarised the in vivo findings of hydrocephalus and the associated pathological changes of brain and craniofacial skeletal tissues with the genetically modified mouse (GMM) models of various genes knocked out in CNCCs. Significantly, the functional gene knockout in Wnt1 expressing cells can lead to hydrocephalus and associated brain and craniofacial skeletal pathologies, irrespective of the ectopic midbrain Wnt1 activation observed in Wnt1-Cre driver mice. However, the specific contributions and underpinning mechanisms of the main structures of the CSF system, including CNCCs-derived choroid plexus, to hydrocephalus pathophysiology are yet to be fully elucidated.
脑积水是一种由于脑脊液（CSF）在脑室中积聚而导致的病理状况，已被认为是新生儿和年轻人中相对常见的脑部异常，无论有无颅面畸形。它可引起身体、行为和认知症状，严重时可能导致死亡。脑积水可由多种潜在病症引起，其多因素性质使得确定单一的病理生理病因具有挑战性。值得注意的是，据报道，在使用Wnt1-Cre的各种基因的颅神经嵴细胞（CNCCs）条件性敲除小鼠模型中，脑积水的发生率相对较高（高达100%），而在不同品系的实验小鼠中，脑积水的自发发生率极低（0.01%至0.86%）。令人惊讶的是，尽管CNCCs在颅面和神经组织的正常发育和病理状况中的重要作用已得到广泛研究和高度认可，但关于脑积水与CNCCs之间联系的报道却很少。在本综述中，除了揭示脑积水的高发生率（5.4%-100%）外，我们主要总结了在各种基因在CNCCs中敲除的转基因小鼠（GMM）模型中脑积水的体内研究结果以及相关的脑和颅面骨骼组织的病理变化。值得注意的是，无论在Wnt1-Cre驱动小鼠中观察到的异位中脑Wnt1激活情况如何，在表达Wnt1的细胞中进行功能性基因敲除均可导致脑积水以及相关的脑和颅面骨骼病变。然而，脑脊液系统主要结构（包括CNCCs衍生的脉络丛）对脑积水病理生理学的具体贡献和潜在机制尚未完全阐明。
