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Role of aquaporins in hydrocephalus: what do we know and where do we stand? A systematic review

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Abstract

Introduction

Glymphatic fluid circulation may be considered the lymphatic system of the brain and the main role of such system seems to be played by aquaporins (AQPs), a family of proteins which regulates water exchange, in particular AQP4 and 1. Alterations of glymphatic fluid circulation through AQPs variations are now emerging as central elements in the pathophysiology of different brain conditions, like hydrocephalus. This systematic review provides an insight about the role of AQPs in hydrocephalus establishment and compensation, investigating their possible role as diagnostic tools or therapeutic targets.

Methods

PubMed database was screened searching for the relevant existing literature in English language published until February 29th 2020, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement.

Results

A total of 40 articles met the inclusion criteria for our systematic analysis. AQP4 resulted the most studied water channel, followed by AQP1. The changes in cerebrospinal fluid (CSF), brain parenchyma and choroid plexus (CP) in different hydrocephalus type were analyzed. Moreover, important pharmacological interactions regarding AQP and molecules or conditions were discussed. A very interesting result is the general consensus on increase of AQP4 in hydrocephalic patients, unless in patients suffering from idiopathic normal pressure hydrocephalus, where AQP4 shows a tendency in reduction.

Conclusion

AQP seem to play a central role in the pathophysiology of hydrocephalus and in its compensation mechanisms. Further studies are required to definitively establish their precise roles and their quantitative changes to allow their utilization as diagnostic tools or therapeutic targets.

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Authors and Affiliations

  1. Unit of Neurosurgery, Ospedale San Gerardo, Azienda Socio Sanitaria Territoriale Monza, Via G. B. Pergolesi 33, 20900, Monza, MB, Italy

    Camilla de Laurentis, Paola Cristaldi, Clarissa Cavandoli, Andrea Trezza, Erik P. Sganzerla, Carlo G. Giussani & Andrea Di Cristofori

  2. Department of Surgery and Medicine, Università degli Studi Milano-Bicocca, Milan, MI, Italy

    Camilla de Laurentis, Paola Cristaldi, Erik P. Sganzerla & Carlo G. Giussani

  3. Unit of Neurology - UOSD Malattie Neurodegenerative, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, MI, Italy

    Andrea Arighi

  4. Dino Ferrari Center - Università degli Studi di Milano, Milan, MI, Italy

    Andrea Arighi

  5. Università degli Studi di Milano, Milan, MI, Italy

    Clarissa Cavandoli

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  1. Camilla de Laurentis
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Concept of the article: AC, CL. Literature search and data analysis: CL, AC. Draft of the article: AC, CL, AA. Critically revision of the article: all authors.

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Correspondence to Andrea Di Cristofori.

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de Laurentis, C., Cristaldi, P., Arighi, A. et al. Role of aquaporins in hydrocephalus: what do we know and where do we stand? A systematic review. J Neurol 268, 4078–4094 (2021). https://doi.org/10.1007/s00415-020-10122-z

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