Aquaporin 4 correlates with apparent diffusion coefficient and hydrocephalus severity in the rat brain: A combined MRI–histological study

Hydrocephalus features include ventricular dilatation and periventricular edema due to transependymal resorption of cerebrospinal fluid (CSF). Aquaporin 4 (AQP4), a water channel protein located at the blood-brain barrier, might facilitate the removal of this excess of water from the parenchyma into the blood. First, we hypothesized a link between AQP4 expression and the severity of hydrocephalus. We further hypothesized that movements of water through AQP4 could affect apparent diffusion coefficient (ADC) measurements. Communicating inflammatory hydrocephalus was induced in 45 rats, and at various stages, magnetic resonance imaging (MRI) was used to measure CSF volume and periventricular ADC, with immunostaining being used to determine periventricular AQP4. We found an up-regulation of periventricular AQP4 in hydrocephalic rats that was strongly correlated with both CSF volume (Pearson=0.87, p<0.00001) and periventricular ADC (Pearson=0.85, p<0.00001). AQP4 were first located on astrocyte endfeet, but later on the whole membrane of astrocytes that became hypertrophic in the most severe and chronic hydrocephalic rats. These results show that AQP4 expression follows an adaptative profile to the severity of hydrocephalus, which is probably a protective response mechanism. They also suggest that ADC, on top of informing about cell sizes and interstitial bulk water, might also indirectly reflect quantitative water channel expression.