Li Yuyuan, Wang Yining, Huang Xingda, Zhang Hao, Guan Youfei, Zhang Xiaoyan
Advanced Institute for Medical Sciences, Dalian Medical University, Dalian, China.
Health Science Center, East China Normal University, Shanghai, China.
Front Neurosci. 2025 Jan 29;19:1518967. doi: 10.3389/fnins.2025.1518967. eCollection 2025.
Water serves as the primary substance in all living cells and is an essential molecule involved in numerous biological processes critical for maintaining homeostasis in the central nervous system (CNS). Disruptions in water balance can occur in conditions such as cerebral edema, where fluid accumulation results in increased intracranial pressure (ICP). Aquaporins (AQPs) are transmembrane proteins that play a vital role in the rapid transport of water across cell membranes. Various subtypes of AQPs (AQP1, AQP3, AQP4, AQP5, AQP6, AQP7, AQP8, AQP9, and AQP11) have been identified in brain tissue. This review summarizes the latest advancements in our understanding of the critical role of AQPs in regulating water transport in brain edema. Abundant evidence indicates that AQP4, the most prevalent AQP in the CNS, regulates brain water transport and contributes to both cytotoxic and vasogenic edema, suggesting that AQP4 may serve as a potential therapeutic target for brain edema. Additionally, some studies have indicated that AQP1 plays a significant role in the formation of cerebrospinal fluid (CSF) and the maintenance of steady-state ICP. However, to date, these findings have not been translated into clinical practice. There is an urgent need to develop specific AQP inhibitors and activators to explore the potential benefits of modulating the functions of AQP1 and AQP4 in the context of brain edema.
水是所有活细胞中的主要物质,是参与众多生物过程的必需分子,对维持中枢神经系统(CNS)的体内平衡至关重要。在脑水肿等情况下会出现水平衡紊乱,其中液体蓄积会导致颅内压(ICP)升高。水通道蛋白(AQP)是跨膜蛋白,在水快速跨细胞膜转运中起重要作用。已在脑组织中鉴定出多种AQP亚型(AQP1、AQP3、AQP4、AQP5、AQP6、AQP7、AQP8、AQP9和AQP11)。本综述总结了我们对AQP在脑水肿中调节水转运的关键作用的最新认识进展。大量证据表明,AQP4是中枢神经系统中最普遍的AQP,调节脑水转运并导致细胞毒性水肿和血管源性水肿,这表明AQP4可能是脑水肿的潜在治疗靶点。此外,一些研究表明,AQP1在脑脊液(CSF)形成和稳态颅内压维持中起重要作用。然而,迄今为止,这些发现尚未转化为临床实践。迫切需要开发特异性AQP抑制剂和激活剂,以探索在脑水肿情况下调节AQP1和AQP4功能的潜在益处。
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