The Blood Brain Barrier

Each portion of the nervous system is separated from the blood (and thus the rest of the body) by a metabolic 'barrier,' which modulates the access of nutrients to and the removal of metabolites from the neurons and glia within it. For the brain and spinal cord, this barrier is termed the 'blood-brain barrier' (BBB; there is also a blood-cerebrospinal fluid (CSF) barrier; CSF is made from blood); for the retina, it is called the 'blood-retinal barrier,' and for peripheral neurons, the 'blood-nerve barrier.' The functions of these barriers are very similar. The focus of the following discussion will be the BBB, because it has been studied the most.

The BBB is located in the endothelial cells that make up the brain's capillaries. Unlike capillaries elsewhere in the body, the endothelial cells of brain capillaries are tightly joined, such that nothing passes into (or out of) brain without passing through these cells. The BBB thus presents a continuous lipid barrier to molecules. One implication is that the ease with which molecules in blood gain access to brain should depend on their lipid solubility: the more lipid soluble, the greater the accessibility to brain by diffusion. However, most molecules of biologic importance to brain are not lipid soluble, and thus do not easily diffuse across lipid membranes into brain. Examples include glucose, amino acids, and water-soluble vitamins. Consequently, endothelial cell membranes must be more than just lipid barriers; indeed, embedded in them are specific transport carriers that mediate the brain uptake of most nutrients.

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