Journal
ULTRASOUND IN MEDICINE AND BIOLOGY
Volume 32, Issue 9, Pages 1399-1409Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.ultrasmedbio.2006.05.015
Keywords
blood-brain barrier; ultrasound; arterioles; transendothelial vesicular traffic; ultrastructural morphometry
Funding
- NCRR NIH HHS [U41RR019703] Funding Source: Medline
- NIBIB NIH HHS [EB 003268, EB 000705] Funding Source: Medline
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Previously, activation of vesicular transport in the brain microvasculature was shown to be one of the mechanisms of focused ultrasound-induced blood-brain barrier (BBB) opening. In the present study, we aimed to estimate the rate of the transendothelial vesicular traffic after focused ultrasound sonication in the rabbit brain, using ultrastructural morphometry and horseradish peroxidase (HRP) as a tracer. In the capillaries, the mean endothelial pinocytotic densities (the number of HRP-containing vesicles per mu m(2) of the cell cytoplasm) were 0.9 and 1.05 vesicles/mu m(2) 1 h after sonication with ultrasound frequencies of 0.69 and 0.26 MHz, respectively. In the arterioles, these densities were 1.63 and 2.43 vesicles/mu m(2), values 1.8 and 2.3 times higher. In control locations, the densities were 0.7 and 0.14 vesicles/mu m(2) for capillaries and arterioles, respectively. A small number of HRP-positive vesicles were observed in the venules. Focal delivery of HRP tracer was also observed in light microscopy. The results indicate that the precapillary microvessels play an important role in macromolecular transcytoplasmic traffic through the ultrasound-induced BBB modulation, which should be considered in the future development of trans-BBB drug delivery strategies.
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