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Elisa E. Konofagou
Postal:
Department of Biomedical Engineering and Department of Radiology Columbia University 1210 Amsterdam Avenue ET 351, MC 8904 New York, New York 10027 USA
Email:
ek2191@columbia.edu
Trespassing the Barrier
of the Brain with Ultrasound
Focused ultrasound is a powerful tool for overcoming the immense hurdles in drug delivery that are posed in brain therapeutics.
The Blood-Brain Barrier Physiology:
Structure and Function
The brain is critical to the function of the whole body. Thus, any compromise of the brain by toxic molecules circulating in the blood could be fatal to the organ- ism. As a consequence, the brain has its own unique defense system to protect against toxic molecules. This defense system is mainly composed of the blood- brain barrier (BBB), which, as its name denotes, is a barrier or “filter” between the blood circulation in the brain and the brain tissue itself. In other words, the brain is protected from toxic molecules more stringently than is the rest of the body because of the BBB.
The BBB constitutes a collection of different cells (Figure 1) that contribute to this structural and functional barrier. Each of these cells has its own function of either transporting a molecule from the blood circulation into the brain tissue or parenchyma or allowing a molecule to diffuse due to its specific size, just as any other filter would do. For example, the most common feature of the BBB are the tight junctions, which are specialized proteins that connect the cells along the inner linings of the blood vessels (also known as “endothelial cells”), thus allow- ing only very small molecules (<400 Da in molecular weight or <1 nm in size) to
Figure 1. The blood-brain barrier (BBB) and its constituents. The lumen is from a capillary of the circulatory system and the surrounding cells con- stitute the BBB. Brain parenchyma represents the tissues of the brain.
cross (Pardridge, 2015). The endo- thelial cells also have membranes that further filter molecules. The combination of the tight junctions and those membranes provide the filtering mechanism of the BBB. Other cells such as astrocytes and pericytes serve as mechanical ab- sorbers and thus provide a protec- tive mechanism of the neurons to any mechanical effect (Abbott et al., 2006).
The BBB and Neurotherapeutics According to the National Center of Health Statistics (http://www. cdc.gov/nchs/fastats/deaths.htm), more than 5.4 million Americans
are currently diagnosed with Alzheimer’s disease, 1 million with Parkinson’s dis- ease, 350,000 with multiple sclerosis, 20,000 with amyotrophic lateral sclerosis (ALS), and 10,000 with brain cancer. Worldwide, these diseases account for more
©2017 Acoustical Society of America. All rights reserved. volume 13, issue 4 | Winter 2017 | Acoustics Today | 21