Altered brain fluid management in a rat model of arterial hypertension

Background: Proper neuronal function is directly dependent on the composition, turnover, and amount of interstitial fluid that bathes the cells. Most of the interstitial fluid is likely to be derived from ion and water transport across the brain capillary endothelium, a process that may be altered in hypertension due to vascular pathologies as endothelial dysfunction and arterial remodelling. In the current study, we investigated the effects of hypertension on the brain for differences in the water homeostasis. Methods: Magnetic resonance imaging (MRI) was performed on a 7T small animal MRI system on male spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) of 10 months of age. The MRI protocol consisted of T2-weighted scans followed by quantitative apparent diffusion coefficient (ADC) mapping to measure volumes of different anatomical structures and water diffusion respectively. After MRI, we assessed the spatial distribution of aquaporin 4 expression around blood vessels. Results: MRI analysis revealed a significant reduction in overall brain volume and remarkably higher cerebroventricular volume in SHR compared to WKY. Whole brain ADC, as well as ADC values of a number of specific anatomical structures, were significantly lower in hypertensive animals. Additionally, SHR exhibited higher brain parenchymal water content. Immunohistochemical analysis showed a profound expression of aquaporin 4 around blood vessels in both groups, with a significantly larger area of influence around arterioles. Evaluation of specific brain regions revealed a decrease in aquaporin 4 expression around capillaries in the corpus callosum of SHR. Conclusion: These results indicate a shift in the brain water homeostasis of adult hypertensive rats