Structural and Diffusion MRI to Study the Effects of Hypertension in Rat Brain Macrostructure and Microstructure

Abstract

Hypertension (HTN) is associated with an increased risk of cardiovascular disease (CVD) and cognitive decline in aging humans, with onset occurring around middle age, and responsible for roughly 7 million deaths worldwide, annually. Prior research has also shown that mid-life HTN is associated with negative effects on brain structure and function in late life. Therefore, it is important to study the symptoms of HTN on the central nervous system as the disease progresses with age, and specifically how this may affect neurological anatomy, development, and function. Animal models are an integral tool in preclinical, translational research of the human body, facilitating greater understanding, treatment, and prevention of diseases such as HTN. The Fischer-344 Cyp1a1-Ren2 transgenic xenobiotic-inducible rat model is an appreciable strain in studies of HTN due to the fact that the induction of increased blood pressure, as induced via the administration of dietary molecule Indole-3-Carbinol (I3C), is reversible, controllable, and dose-dependent in magnitude. The purpose of this study was to investigate the longitudinal effects of induced HTN in macrostructural and microstructural neuroanatomy of F344 Cyp1a1-Ren2 transgenic rats through the use of noninvasive diffusion-weighted MRI (dMRI) and imaging analyses. Results of this study show that even in the face of sustained increases in blood pressure and end-organ damage in the heart and kidney, a majority of the brain remained unaffected in terms of volume and microstructural characteristics. This indicates the presence of an intrinsic, protective mechanism of the brain in this model, forestalling the onset of detrimental effects of HTN on brain structure and function.