Blood-Brain Barrier Disruption and Perivascular Beta-Amyloid Accumulation in the Brain of Aged Rats with Spontaneous Hypertension: Evaluation with Dynamic Contrast-Enhanced Magnetic Resonance Imaging.

OBJECTIVE

Whether blood-brain barrier (BBB) disruption induced by chronic spontaneous hypertension is associated with beta-amyloid (Aβ) accumulation in the brain remains poorly understood. The purpose of this study was to investigate the relationship between BBB disruption and Aβ influx and accumulation in the brain of aged rats with chronic spontaneous hypertension.

MATERIALS AND METHODS

Five aged spontaneously hypertensive rats (SHRs) and five age-matched normotensive Wistar-Kyoto (WKY) rats were studied. The volume transfer constant (K) obtained from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was used to evaluate BBB permeability in the hippocampus and cortex . The BBB tight junctions, immunoglobulin G (IgG), Aβ, and amyloid precursor protein (APP) in the hippocampus and cortex were examined with immunohistochemistry.

RESULTS

As compared with WKY rats, the K values in the hippocampus and cortex of the SHRs increased remarkably (0.316 ± 0.027 min vs. 0.084 ± 0.017 min, < 0.001 for hippocampus; 0.302 ± 0.072 min vs. 0.052 ± 0.047 min, < 0.001 for cortex). Dramatic occludin and zonula occludens-1 losses were detected in the hippocampus and cortex of SHRs, and obvious IgG exudation was found there. Dramatic Aβ accumulation was found and limited to the area surrounding the BBB, without extension to other parenchyma regions in the hippocampus and cortex of aged SHRs. Alternatively, differences in APP expression in the hippocampus and cortex were not significant.

CONCLUSION

Blood-brain barrier disruption is associated with Aβ influx and accumulation in the brain of aged rats with chronic spontaneous hypertension. DCE-MRI can be used as an effective method to investigated BBB damage.