JBM  Vol.1 No.2 , October 2013
The effects of ultrasound on blood-brain barrier
ABSTRACT

The brain is protected from the entry of foreign substances by blood-brain barrier (BBB), but becomes a barrier while chemotherapy is needed for the brain diseases. Ultrasound with microbubbles (MBs) has been shown to noninvasively increase the permeability of the BBB in the normal tissue and brain tumor. The real mechanism for disruption is still unknown. Hemorrhage was usually found in the sonicated region of the brain. Thus, treatment safety is the primary concern when considering clinical application of BBB disruption induced by ultrasound in the presence of MBs. Here we investigate the effects of ultrasound on the permeability of BBB whether the MBs were administered. The data reveals that Evans blue (EB) accumulation was highest in the brain after sonication with MBs. However, the permeability of BBB also can be significantly increased by ultrasound alone. These results demonstrated that noninvasive disruption of BBB by ultrasound alone with no damage is possible.


Cite this paper
Yang, F. and Lin, W. (2013) The effects of ultrasound on blood-brain barrier. Journal of Biosciences and Medicines, 1, 10-13. doi: 10.4236/jbm.2013.12003.
References
[1]   Abbott, N.J. and Romero, I.A. (1996) Transporting therapeutics across the blood-brain barrier. Trends in Molecular Medicine, 2, 106-113. http://dx.doi.org/10.1016/1357-4310(96)88720-X

[2]   Yang, F.Y., Lin, Y.S., Kang, K.H. and Chao, T.K. (2011) Reversible blood-brain barrier disruption by repeated transcranial focused ultrasound allows enhanced extravasation. Journal of Controlled Release, 150, 111-116. http://dx.doi.org/10.1016/j.jconrel.2010.10.038

[3]   Yang, F.Y., Wang, H.E., Lin, G.L., Teng, M.C., Lin, H.H., Wong, T.T. and Liu, R.S. (2011) Micro-SPECT/ CT-based pharmacokinetic analysis of 99mTc-diethy- lenetriaminepentaacetic acid in rats with blood-brain barrier disruption induced by focused ultrasound. Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine, 52, 478-484.

[4]   Yang, F.Y., Wong, T.T., Teng, M.C., Liu, R.S., Lu, M., Liang, H.F. and Wei, M.C. (2012) Focused ultrasound and interleukin-4 receptor-targeted liposomal doxorubicin for enhanced targeted drug delivery and antitumor effect in glioblastoma multiforme. Journal of Controlled Release, 160, 652-658. http://dx.doi.org/10.1016/j.jconrel.2012.02.023

[5]   Hynynen, K., McDannold, N., Sheikov, N.A., Jolesz, F.A., Vykhodtseva, N. (2005) Local and reversible blood- brain barrier disruption by noninvasive focused ultrasound at frequencies suitable for trans-skull sonications. Neuroimage, 24, 12-20. http://dx.doi.org/10.1016/j.neuroimage.2004.06.046

[6]   Yang, F.Y. and Lee, P.Y. (2012) Efficiency of drug delivery enhanced by acoustic pressure during blood-brain barrier disruption induced by focused ultrasound, International Journal of Nanomedicine, 7, 2573-2582. http://dx.doi.org/10.2147/IJN.S31675

[7]   Hynynen, K. (2008) Ultrasound for drug and gene delivery to the brain. Advanced Drug Delivery Reviews, 60, 1209-1217. http://dx.doi.org/10.1016/j.addr.2008.03.010

[8]   Yang, F.Y., Wang, H.E., Lin, G.L., Lin, H.H. and Wong, T.T. (2012) Evaluation of the increase in permeability of the blood-brain barrier during tumor progression after pulsed focused ultrasound. International Journal of Nanomedicine, 7, 723-730. http://dx.doi.org/10.2147/IJN.S28503

[9]   Yang, F.Y., Chen, C.C., Kao, Y.H., Chen, C.L., Ko, C.E., Horng, S.C. and Chen, R.C. (2013) Evaluation of dose distribution of molecular delivery after blood-brain barrier disruption by focused ultrasound with treatment planning. Ultrasound in Medicine & Biology, 39, 620-627. http://dx.doi.org/10.1016/j.ultrasmedbio.2012.11.027

[10]   Kroll, R.A. and Neuwelt, E.A. (1998) Outwitting the blood-brain barrier for therapeutic purposes: Osmotic opening and other means. Neurosurgery, 42, 1083-1099; discussion, 1099-1100. http://dx.doi.org/10.1097/00006123-199805000-00082

[11]   Pardridge, W.M. (2002) Drug and gene delivery to the brain: The vascular route. Neuron, 36, 555-558. http://dx.doi.org/10.1016/S0896-6273(02)01054-1

[12]   McDannold, N., Vykhodtseva, N., Jolesz, F.A. and Hynynen, K. (2004) MRI investigation of the threshold for thermally induced blood-brain barrier disruption and brain tissue damage in the rabbit brain. Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine/Society of Magnetic Resonance in Medicine, 51, 913-923.

 
 
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