The blood-brain barrier, which controls the chemical trafficking and brain, can be even more complex than previously thought. Certain compounds that seem to penetrate the entire brain, as indicated by the analysis of the brain, are caught by a second line of defense. Experts say the findings, reported in the February American Journal of Neuroradiology , underline the problem of providing drugs against a variety of brain diseases such as stroke, brain tumors and neurodegenerative diseases.
The blood-brain barrier is a filter at the base of your skull, rather it is a coating of cells that line hundreds of kilometers of blood vessels reach every crevice of the skull. These cells, called endothelial cells, are cemented with gluelike substances in structures called tight junctions. Normally only small molecules soluble in lipids can seep through this barrier. Glucose and other substances needed are the shuttle through specific conveyor systems. For anything else, such as drugs or virus particles designed to carry therapeutic genes, scientists must resort to a trick: Inject a concentrated sugar solution makes endothelial cells shrink, temporary opening pores between the cells
using this technique. The team neurosurgeon Edward Neuwelt at Oregon Health Sciences University and the Veterans Administration Medical Center in Portland has undertaken to develop a noninvasive means of monitoring the distribution of potential drugs. They injected rats with two types of iron oxide grains sugar-coated, the size of virus particles commonly used for gene therapy. The team visualized particles with MRI, suggesting that both compounds evenly distributed throughout the brain. But when Neuwelt watched some preparations of brain slices under the microscope at a higher resolution, was surprised: A compound had spent endothelial cells, but was stuck in a complex mesh of sugar and protein fibers, called the basement membrane surrounding the blood vessels. With most standard imaging techniques, Neuwelt said, trapping some compounds in the "web of the basement membrane" could give "false view that you got the uniform delivery, when in fact you do not have it. "
" the study shows that there is more to the blood-brain barrier tight junctions. It challenges mainstream thinking, "says neuroscientist Thomas Jacobs of the National Institute of Neurological Disorders and Stroke in Bethesda, Maryland. The findings, Jacobs said, emphasize the importance of setting aside more resources for the study of drug administration, the "Achilles heel" of the brain therapies. Neuwelt agreement: "The industry is spending hundreds of millions of dollars to develop new drugs [for the brain], yet virtually nothing about how to get there" The next step, he adds, is. "why some particles pass through and others do not."
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