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Fluids and Barriers of the CNS
Published in: Fluids and Barriers of the CNS 1/2010

Open Access 01-12-2010 | Research

Hydrocephalus induces dynamic spatiotemporal regulation of aquaporin-4 expression in the rat brain

Authors: Anders D Skjolding, Ian J Rowland, Lise V Søgaard, Jeppe Praetorius, Milena Penkowa, Marianne Juhler

Published in: Fluids and Barriers of the CNS | Issue 1/2010

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Abstract

Background

The water channel protein aquaporin-4 (AQP4) is reported to be of possible major importance for accessory cerebrospinal fluid (CSF) circulation pathways. We hypothesized that changes in AQP4 expression in specific brain regions correspond to the severity and duration of hydrocephalus.

Methods

Hydrocephalus was induced in adult rats (~8 weeks) by intracisternal kaolin injection and evaluated after two days, one week and two weeks. Using magnetic resonance imaging (MRI) we quantified lateral ventricular volume, water diffusion and blood-brain barrier properties in hydrocephalic and control animals. The brains were analysed for AQP4 density by western blotting and localisation by immunohistochemistry. Double fluorescence labelling was used to study cell specific origin of AQP4.

Results

Lateral ventricular volume was significantly increased over control at all time points after induction and the periventricular apparent diffusion coefficient (ADC) value significantly increased after one and two weeks of hydrocephalus. Relative AQP4 density was significantly decreased in both cortex and periventricular region after two days and normalized after one week. After two weeks, periventricular AQP4 expression was significantly increased. Relative periventricular AQP4 density was significantly correlated to lateral ventricular volume. AQP4 immunohistochemical analysis demonstrated the morphological expression pattern of AQP4 in hydrocephalus in astrocytes and ventricular ependyma. AQP4 co-localized with astrocytic glial fibrillary acidic protein (GFAP) in glia limitans. In vascular structures, AQP4 co-localized to astroglia but not to microglia or endothelial cells.

Conclusions

AQP4 levels are significantly altered in a time and region dependent manner in kaolin-induced hydrocephalus. The presented data suggest that AQP4 could play an important neurodefensive role, and may be a promising future pharmaceutical target in hydrocephalus and CSF disorders.
Appendix
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Metadata
Title
Hydrocephalus induces dynamic spatiotemporal regulation of aquaporin-4 expression in the rat brain
Authors
Anders D Skjolding
Ian J Rowland
Lise V Søgaard
Jeppe Praetorius
Milena Penkowa
Marianne Juhler
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Fluids and Barriers of the CNS / Issue 1/2010
Electronic ISSN: 2045-8118
DOI
https://doi.org/10.1186/1743-8454-7-20

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