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Aquaporins in Brain Disease, 2nd Edition
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Aquaporins in Brain Disease, 2nd Edition

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (20 June 2025) | Viewed by 871

Special Issue Editors

Prof. Dr. Pablo García-Miranda

E-Mail Website
Guest Editor
Department of Physiology, University of Seville, 41009 Seville, Spain
Interests: aquaporins; neurological biomarkers; NMO; blood–brain barrier; gut–brain axis
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Miriam Echevarría

E-Mail Website
Guest Editor
Department of Physiology and Biophysics, University of Seville, 41009 Seville, Spain
Interests: aquaporins; CNS; neuroscience; cerebrospinal fluid homeostasis; hydrocephalus; NMO
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The expression of several aquaporins has been reported in the brain of mammals. Their functioning, particularly for AQP4 and AQP1, has been associated with facilitating the flow of water through brain compartments (blood, interstitial space and CSF) and plays an important role in CSF homeostasis. Recent findings revealed that the glymphatic system facilitates the clearance of fluid and waste from the brain through a mechanism that depends on the presence of AQP4 in the perivascular astroglia. Consistent with this, the loss or mislocalization of astrocyte AQP4 from perivascular locations has been observed in animal and human studies, allowing for the association of this AQP with degenerative diseases such as idiopathic normal pressure hydrocephalus (iNPH), Parkinson’s disease (PD) and Alzheimer’s disease (AD). Furthermore, in different brain pathological conditions, ranging from acute brain injuries (stroke, traumatic brain injury), to edema and autoimmune demyelinating disease such as NMO, the key role of AQP4 was unveiled. Previous evidence indicates that brain AQPs may be involved in cell migration, angiogenesis and human brain tumor growth, making these proteins potential therapeutic targets by antagonizing their biological activity. To date, no specific therapeutic agents have been developed to inhibit or enhance water flow through these channels. However, experimental results strongly underline the importance of this topic for future investigations. Papers related to any aspect of aquaporin physiology and expression in the CNS, biochemistry and molecular biology aspects of brain AQPs, neurological diseases and/or animals model relating AQPs to brain pathology will be considered for this Special Issue. Experimental and up-to-date review articles and commentaries are also welcome.

Prof. Dr. Pablo García-Miranda
Prof. Dr. Miriam Echevarría
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • edema
  • hydrocephalus
  • NMO
  • neurodegenerative diseases
  • iNPH
  • CSF
  • glymphatic system
  • brain tumors

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Related Special Issue

Published Papers (2 papers)

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Research

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17 pages, 8254 KiB  
Article
Aquaporins in the Capillaries of the Dura Mater of Pigs
by Slavica Martinović, Dinko Smilović, Boris Pirkić, Petra Dmitrović, Leonarda Grandverger and Marijan Klarica
Int. J. Mol. Sci. 2025, 26(15), 7653; https://doi.org/10.3390/ijms26157653 - 7 Aug 2025
Viewed by 199
Abstract
Dura mater plays a critical role in neurofluid homeostasis, yet comparative data on capillary network density and organization between cranial and spinal regions remain limited. This study addresses this gap by systematically analyzing capillary architecture and aquaporin (AQP) expression in porcine cranial (parietal, [...] Read more.
Dura mater plays a critical role in neurofluid homeostasis, yet comparative data on capillary network density and organization between cranial and spinal regions remain limited. This study addresses this gap by systematically analyzing capillary architecture and aquaporin (AQP) expression in porcine cranial (parietal, falx) and spinal dura mater. Immunofluorescence labeling and confocal microscopy were used to assess capillary density, spatial distribution, and AQP1/AQP4 expression patterns across over 1000 capillaries in these regions. Cranial dura exhibited a 3–4 times higher capillary density compared to spinal dura, with capillaries predominantly localized to meningeal–dural border cell interfaces in cranial regions and a more dispersed distribution in spinal dura. Both AQP1 and AQP4 were detected as discrete clusters within capillary walls, with higher expression in cranial compared to spinal dura. Lymphatic vessels (PDPN-positive) were also observed adjacent to capillaries, supporting a dual-system model for fluid and waste exchange. These findings highlight the dura’s region-specific vascular specialization, with cranial regions favoring dense, structured capillary networks suited for active fluid exchange. This work establishes a foundation for investigating capillary-driven fluid dynamics in pathological states like subdural hematomas or hydrocephalus. Full article
(This article belongs to the Special Issue Aquaporins in Brain Disease, 2nd Edition)
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Review

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18 pages, 1835 KiB  
Review
Aquaporin-4 in Stroke and Brain Edema—Friend or Foe?
by Cecilia Alejandra García Ríos and Jose E. Leon-Rojas
Int. J. Mol. Sci. 2025, 26(17), 8178; https://doi.org/10.3390/ijms26178178 (registering DOI) - 23 Aug 2025
Abstract
Stroke is a leading global cause of mortality and long-term disability, with cerebral edema constituting a major contributor to early neurological deterioration and poor outcomes. Aquaporin-4 (AQP4), the predominant water channel in the central nervous system, plays a paradoxical role in stroke-related brain [...] Read more.
Stroke is a leading global cause of mortality and long-term disability, with cerebral edema constituting a major contributor to early neurological deterioration and poor outcomes. Aquaporin-4 (AQP4), the predominant water channel in the central nervous system, plays a paradoxical role in stroke-related brain edema, facilitating both the formation and clearance of excess fluid depending on the pathological context. This review explores the biphasic function of AQP4 across cytotoxic and vasogenic edema, emphasizing its dynamic regulation, subcellular localization, and implications for therapeutic intervention. Evidence from rodent models shows that AQP4 exacerbates cytotoxic edema in acute ischemia by promoting intracellular water influx into astrocytes, whereas in vasogenic edema, it supports fluid reabsorption and glymphatic clearance, thereby alleviating brain swelling. Human studies corroborate AQP4 upregulation in infarcted regions and suggest a potential role for AQP4 polymorphisms and circulating levels as biomarkers of stroke severity and outcome, although larger cohorts and more robust methodological designs are needed. This review also discusses emerging pharmacological strategies to modulate AQP4 activity, including inhibitors, trafficking modulators, and gene-targeted delivery systems, while highlighting challenges in achieving phase-specific modulation. Given its central role in both injury and recovery, AQP4 emerges as a promising yet complex therapeutic target for personalized management of stroke-induced brain edema. Future directions include real-time imaging of AQP4 function, genotype-stratified clinical trials, and integration of AQP4 modulation with current stroke treatment protocols. Full article
(This article belongs to the Special Issue Aquaporins in Brain Disease, 2nd Edition)
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