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BLOOD BRAIN BARRIER


BLOOD-BRAIN BARRIER
The blood-brain barrier (BBB) is the cellular interface between the blood and the CNS. It serves to protect the brain from unwanted intrusion by many large molecules and potentially toxic substances and to maintain the interstitial fluid environment to ensure optimal functioning of the neurons and their associated glial cells. The major cellular basis for the BBB consists of the capillary endothelial cells which have an elaborate network of tight junctions; these tight junctions restrict access by many large molecules, including many drugs, to the CNS. Endothelial cells in the CNS also exhibit a low level of pinocytotic activity across the cell, providing selected specific carrier systems for the transport of essential substrates of energy production and amino acid metabolism into the CNS. Astrocytic end foot processes abut the endothelial cells and their basement membranes; these processes help to transfer important metabolites from the blood to neurons and can influence the expression of some specific gene products in the endothelial cells. These astrocytic processes also can remove excess K+ and some neurotransmitters from the interstitial fluid.



CLINICAL POINT
The BBB, anatomically consisting mainly of the capillary tight junctions of the vascular endothelial cells, serves to protect the CNS from the intrusion of large molecules and potentially damaging agents from the peripheral circulation. The neurons need protection of their ionic and metabolic environment, which is aided by glial cells and the BBB. There are selected areas (windows on the brain) where the BBB is not present, such as the median eminence, the area postrema, the organum vasculosum of the lamina terminalis, and others, and where specialized cells can sample the peripheral circulation and can initiate corrective brain mechanisms to protect the neuronal environment. The presence of the BBB presents a challenge for pharmacotherapy aimed at the CNS; many antibiotics and other agents will not penetrate the BBB and must be coupled to a carrier molecule that does cross or must be injected intrathecally. In some pathological circumstances, such as the presence of a brain tumor, neuronal degeneration resulting from a neurodegenerative disease, the presence of a high concentration of a solute, or a stroke, the BBB is disrupted extensively, exposing the internal CNS milieu to molecules in the peripheral circulation. Therapeutic strategies now are being tested that will achieve transport of desired pharmacotherapeutic agents across the BBB and will protect the brain from unwanted disruption of the BBB in pathological circumstances.