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Blood-brain barrier

The blood vessels comprising the brain microvasculature form an effective barrier between the blood and the cells of the brain. Unlike the blood vessels in the periphery of the body where solutes pass freely through fenestrae, the brain capillaries lack such openings and also have tight junctions between endothelial cells (E) eliminating intercellular transport. The principal barrier is formed by endothelial cells and many of the specialized properties of these cells are induced by cells proximal to the blood vessels in the brain. These cells include astrocytes (A), pericytes (P), and neurons (Neu). Interestingly, neural stem/progenitor cells (NPC) are also found in close proximity to the brain vasculature.

Figure 1

A large stumbling block in the treatment of neurological disease is the effective delivery of therapeutic agents to the brain. Invasive delivery strategies that require neurosurgery include the implantation of polymer matrices infused with drug or the injection of drug directly into brain cavities known as ventricles. Unless the treatment site is highly localized, these methods are generally unsuccessful because distribution of the drug into the brain matter is dependent on simple molecular diffusion and a very limited treatment volume results. The blood vessels that supply the blood and nutrients to the brain are particularly well suited for such non-invasive delivery of drugs to the brain. Over 400 miles of these capillaries perfuse the human brain and form an effective transport surface area of around 20 m2. In addition, in contrast to invasive delivery methods, the inter-capillary spacing is such that molecular diffusion provides for a comprehensive volume of treatment.