Effects of chronic hypertension and acute cerebral ischemia on blood-brain barrier permeability, brain water content, and cerebral blood volume using MRI Public Deposited

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  • March 21, 2019
  • Zhai, Guihua
    • Affiliation: School of Medicine, UNC/NCSU Joint Department of Biomedical Engineering
  • The process of stroke alters the vascular physiology of the brain. In this dissertation, we have focused on the assessment of cerebrovascular alterations under two ischemic conditions: chronic hypertension with increased cerebral blood perfusion pressure (CPP) and transient focal cerebral ischemia with decreased CPP via the stroke-prone spontaneous hypertensive rats (SHRsp) model and the suture model, respectively. Based on these two models, the temporal evolutions of water content, permeability of BBB and cerebral blood volume (CBV), were monitored using magnetic resonance imaging (MRI). In SHRsp rats, there was no significant water content increase before BBB breakdown, indicating the vasogenic nature of the edema. A weak linear relationship was found between the water content and the permeability to Gd-DTPA during edema development after BBB breakdown, suggesting that the movement of water into brain tissue could have been facilitated by the increase in cerebrovascular permeability to such small molecules as Gd-DTPA. In addition, our results showed that, in SHRsp rats, the occurrence of BBB breakdown was no later than the presence of hemorrhage and the decrease of CBV under the symptoms of weight loss and enlarged ventricles. In a suture model of 90 min occlusion, while BBB permeability followed a biphasic pattern, the water content showed an increasing trend. BBB leakage did not play an important role in water content increase out to at least 6hr after reperfusion. After that, BBB breakdown worsened the edema formation. When permeability was recovered at 24 hr after reperfusion, water content reached its maximal value of the study period. In conclusion, though both chronic hypertension with increased CPP or acute ischemia with decreased CPP can result in BBB breakdown and edema development, the stroke development patterns are different under these two conditions. Our results shed some light on the roles of BBB breakdown in edema formation, may help to evaluate and monitor the effectiveness of therapeutic intervention, and may aid the development of new therapies targeted at maintainance of the BBB.
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  • Lin, Weili
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