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水通道蛋白在脑水转运和水肿中的作用。

Role of aquaporins in brain water transport and edema.

作者信息

Li Yuyuan, Wang Yining, Huang Xingda, Zhang Hao, Guan Youfei, Zhang Xiaoyan

机构信息

Advanced Institute for Medical Sciences, Dalian Medical University, Dalian, China.

Health Science Center, East China Normal University, Shanghai, China.

出版信息

Front Neurosci. 2025 Jan 29;19:1518967. doi: 10.3389/fnins.2025.1518967. eCollection 2025.


DOI:10.3389/fnins.2025.1518967
PMID:39944892
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11814447/
Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cfe/11814447/a6a60dd08460/fnins-19-1518967-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cfe/11814447/3c4a60b13af1/fnins-19-1518967-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cfe/11814447/b1e68cac95fc/fnins-19-1518967-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cfe/11814447/cd1aab90f604/fnins-19-1518967-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cfe/11814447/6ceaa42d2a5f/fnins-19-1518967-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cfe/11814447/a6a60dd08460/fnins-19-1518967-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cfe/11814447/3c4a60b13af1/fnins-19-1518967-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cfe/11814447/b1e68cac95fc/fnins-19-1518967-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cfe/11814447/cd1aab90f604/fnins-19-1518967-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cfe/11814447/6ceaa42d2a5f/fnins-19-1518967-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cfe/11814447/a6a60dd08460/fnins-19-1518967-g0005.jpg

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[8]
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[9]
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[10]
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引用本文的文献

[1]
Aquaporins in the Capillaries of the Dura Mater of Pigs.

Int J Mol Sci. 2025-8-7

[2]
Glymphatic System Dysfunction in Elderly Patients with Late-Onset Epilepsy and Comorbid Chronic Insomnia Revealed by Diffusion Tensor Imaging Along the Perivascular Space (DTI-ALPS).

Neuropsychiatr Dis Treat. 2025-8-4

[3]
Aquaporins in Acute Brain Injury: Insights from Clinical and Experimental Studies.

Biomedicines. 2025-6-7

本文引用的文献

[1]
Aquaporins: Gatekeepers of Fluid Dynamics in Traumatic Brain Injury.

Int J Mol Sci. 2024-6-14

[2]
Modelling midline shift and ventricle collapse in cerebral oedema following acute ischaemic stroke.

PLoS Comput Biol. 2024-5

[3]
Glymphatic System Impairment Contributes to the Formation of Brain Edema After Ischemic Stroke.

Stroke. 2024-5

[4]
(S)-roscovitine, a CDK inhibitor, decreases cerebral edema and modulates AQP4 and α1-syntrophin interaction on a pre-clinical model of acute ischemic stroke.

Glia. 2024-2

[5]
Characterization of Vasogenic and Cytotoxic Brain Edema Formation After Experimental Traumatic Brain Injury by Free Water Diffusion Magnetic Resonance Imaging.

J Neurotrauma. 2024-2

[6]
Evaluation of bumetanide as a potential therapeutic agent for Alzheimer's disease.

Front Pharmacol. 2023-8-4

[7]
The absence of AQP4/TRPV4 complex substantially reduces acute cytotoxic edema following ischemic injury.

Front Cell Neurosci. 2022-12-8

[8]
Bumetanide Rescues Aquaporin-4 Depolarization via Suppressing β-Dystroglycan Cleavage and Provides Neuroprotection in Rat Retinal Ischemia-Reperfusion Injury.

Neuroscience. 2023-2-1

[9]
Altered Expression of AQP1 and AQP4 in Brain Barriers and Cerebrospinal Fluid May Affect Cerebral Water Balance during Chronic Hypertension.

Int J Mol Sci. 2022-10-14

[10]
Cellular changes at the glia-neuro-vascular interface in definite idiopathic normal pressure hydrocephalus.

Front Cell Neurosci. 2022-9-2

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