Assessment of blood-brain barrier injury in hypertensive CSVD by 11.7TMR T1mapping and microvascular pathologic changes

Abstract

We used spontaneously hypertensive rats (SHR) as a hypertensive cerebral small vessel disease (CSVD) model to quantify blood-brain barrier (BBB) disruption by 11.7TMR T1mapping and to investigate white matter lesions and microangiopathy in CSVD. Male SHR were used as a hypertensive CSVD animal model and normotensive Wistar-Kyoto rats (WKY) were used as a control model. After 18 weeks, the rats did the Morris water maze test were evaluated, blood-brain barrier (BBB) integrity were evaluated by using Bruker 11.7T MR T1 mapping. ITK-SNAP software was used to measure hippocampal volume. Then, pathological analysis was carried out on rats, myelin integrity, vascular permeability and microvessel density were assessed by immunohistochemistry. Our data showed that hypertensive CSVD model exhibited decreased memory function, BBB leakage could be detected differently in different brain regions, and T1 values of the hippocampus showed the greatest drop than other areas. Furthermore, the pathological changes in small vessels were more extensive, average optical density of myelin basic protein (MBP) in the white matter of SHR group was significantly reduced, moreover, VEGFR2 immunoreactivity scores (IRS) and CD34-assessed MVD in SHR group were significantly higher than WKY group. We find different parts of the brain tissues have different degrees of BBB leakage, hippocampal atrophy and hippocampal volume were decreased in hypertensive CSVD by using T1 Mapping. Loss of myelin integrity, vascular permeability increased and microangiopathy may contribute to hypertensive-related BBB functional deficits in CSVD model.