Loss of aquaporin-4 impairs cerebrospinal fluid solute clearance through cerebrospinal fluid drainage pathways

Daisuke Kato; Hiroyuki Kameda; Naoya Kinota; Takaaki Fujii; Bai Xiawei; Zhou Simi; Yoshiki Takai; Simon Chau; Yoshiki Miyasaka; Tomoji Mashimo; Yoichiro Abe; Masato Yasui; Kazuyuki Minowa; Kohsuke Kudo

doi:10.1038/s41598-024-79147-y

Loss of aquaporin-4 impairs cerebrospinal fluid solute clearance through cerebrospinal fluid drainage pathways

Sci Rep. 2024 Nov 14;14(1):27982. doi: 10.1038/s41598-024-79147-y.

Authors

Daisuke Kato^{1

2}, Hiroyuki Kameda^{3

4}, Naoya Kinota^{1

2}, Takaaki Fujii^{1

2}, Bai Xiawei², Zhou Simi², Yoshiki Takai^{5

6}, Simon Chau⁷, Yoshiki Miyasaka⁸, Tomoji Mashimo⁹, Yoichiro Abe¹⁰, Masato Yasui⁷, Kazuyuki Minowa¹¹, Kohsuke Kudo^{1

2}

Affiliations

¹ Department of Diagnostic and Interventional Radiology, Hokkaido University Hospital, Sapporo, Japan.
² Department of Diagnostic Imaging, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
³ Department of Diagnostic and Interventional Radiology, Hokkaido University Hospital, Sapporo, Japan. h_kameda@med.hokudai.ac.jp.
⁴ Department of Radiology, Faculty of Dental Medicine, Hokkaido University, Sapporo, Japan. h_kameda@med.hokudai.ac.jp.
⁵ Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, Japan.
⁶ Department of Pathology, Tohoku University Hospital, Sendai, Japan.
⁷ Department of Pharmacology, Keio University School of Medicine, Tokyo, Japan.
⁸ Laboratory of Reproductive Engineering, Institute of Experimental Animal Sciences, Osaka University Medical School, Suita, Japan.
⁹ Division of Animal Genetics, Laboratory Animal Research Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
¹⁰ Department of Pharmacology, Keio University School of Medicine, Tokyo, Japan. yoabe@a6.keio.jp.
¹¹ Department of Radiology, Faculty of Dental Medicine, Hokkaido University, Sapporo, Japan.

Abstract

The aquaporin-4 (AQP4) water channel is essential in neurofluid dynamics. AQP4 loss impairs solute exchange between the cerebrospinal fluid (CSF) and interstitial fluid (ISF). However, whether AQP4 expression affects solute clearance from the CSF space to the extracranial space remains unclear. This study aimed to investigate this using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) following the intrathecal administration of gadolinium-based contrast agents (GBCAs) to AQP4 knockout (KO) rats. AQP4 KO rats showed reduced efflux of intrathecal GBCAs to the extracranial spaces through CSF drainage pathways and increased retention of intrathecal GBCAs in the CSF space compared with the controls. These results suggest that AQP4 loss impairs solute clearance from the CSF space to the extracranial spaces via the CSF drainage pathways. This study revealed a close relationship between AQP4 expression and CSF solute clearance, contributing to a better understanding of the function of AQP4 in neurofluid dynamics.

Keywords: Aquaporin-4; Dynamic contrast-enhanced MRI; Glymphatic System; Neurofluid.

MeSH terms

Animals
Aquaporin 4* / genetics
Aquaporin 4* / metabolism
Cerebrospinal Fluid* / metabolism
Contrast Media*
Extracellular Fluid / metabolism
Gadolinium
Magnetic Resonance Imaging* / methods
Male
Rats

Substances

Aquaporin 4
Contrast Media
Aqp4 protein, rat
Gadolinium