A timeline study on vascular co-morbidity induced cerebral endothelial dysfunction assessed by perfusion MRI
Bram Callewaert, Willy Gsell, Marleen Lox, Uwe Himmelreich, Elizabeth A. V. Jones
Abstract
Endothelial dysfunction is considered a key element in the early pathogenesis of neurodegenerative disorders. Dysfunction of the cerebral endothelial cells can result in dysregulation of cerebral perfusion and disruption of the Blood Brain Barrier (BBB), leading to brain damage, neurodegeneration and cognitive decline. It has been shown that the presence of modifiable risk factors exacerbates endothelial dysfunction. This study primarily aimed to identify which among various perfusion MRI methodologies could be effectively utilized to non-invasively identify early pathological alterations as a result of endothelial dysfunction. We compared these perfusion MRI measurements to invasive immunohistochemistry to detect early pathological alterations in the cerebral vasculature of a rat model of multiple cardiovascular co-morbidities (the ZSF1 Obese rat) at several stages of the cerebrovascular pathology. We observed cerebral hyperperfusion, expressed by increased Cerebral Blood Flow (CBF) and increased BBB permeability in the ZSF1 Obese rats, at an early stage of disease development. The increase in CBF observed with Arterial Spin Labeling (ASL) was lost during later stages of disease progression. These findings are in line with recent clinical findings in early stages of Alzheimer's disease (AD), that also show early increases in CBF. • Cerebral hyperperfusion detected by ASL in ZSF1-O rats at 20 weeks. • Hippocampus, shows a more significant increase in CBF than other regions. • Increased BBB permeability and increased CBF coincide in ZSF1-O rats. • Functional alterations precede morphological changes in vascular network. • ASL could be a diagnostic tool for early detection of neurodegenerative disorders.