Abstract
BackgroundThe 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.MethodsHydrocephalus 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.ResultsLateral 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.ConclusionsAQP4 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.
Highlights
The water channel protein aquaporin-4 (AQP4) is reported to be of possible major importance for accessory cerebrospinal fluid (CSF) circulation pathways
MR-imaging Lateral ventricular volume Quantification of lateral ventricular volume by in vivo magnetic resonance imaging (MRI) showed failed induction of hydrocephalus in three animals belonging to the two-week group
Significant differences occurred in the periventricular regions of interest (ROIs) between the apparent diffusion coefficient (ADC) values of control and both one-week and twoweek groups (Kruskal-Wallis, p < 0.05) but not in the 2-day group
Summary
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. Aquaporins (AQP) are cellular transmembrane proteins with a central pore [7]. This pore is specific to the passage of water molecules exclusively in the orthodox aquaporins, while aquaglyceroporins are permeable to water and other small uncharged molecules such as glycerol, urea and lactate [8,9]. In this study we hypothesized that changes in AQP4 expression in specific brain regions correspond to the severity and duration of hydrocephalus. Our objective was to study the spatiotemporal changes in brain AQP4 expression during experimental hydrocephalus relative to healthy physiological conditions
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