Biology of the Blood-Brain and Blood-Brain Tumor Barriers

The blood-brain barrier (BBB) provides the central nervous system (CNS) with a privileged environment by blocking entry of toxic substances, maintaining optimal concentrations of physiologic molecules, and actively eliminating unwanted substances such as metabolic by-products. The normal BBB is composed of a continuous layer of endothelial cells, constituting the luminal surface of more than 99% of the capillaries of the brain and spinal cord. These cells lack fenestrations and have high resistance tight junctions, which (along with adjacent components of the Neurovascular Unit (NVU)) greatly limit the free passage of molecules. The capillary endothelium within brain tumors has been called the "blood-brain tumor barrier." This chapter provides a general introduction to BBB-related cellular and molecular biology, physiology, and some relevant therapeutic issues. Topics discussed in this chapter include recent information related to immunology and the BBB, cerebral microdialysis, glioma stem cells, and the "BBB on a chip." While new strategies are continually being developed, the clinician's ability to administer safe and effective drugs that cross the BBB continues to be a critical issue for patients with malignant gliomas and brain micrometastases.