Blood-brain barrier transmembrane diffusion

The mechanism of uptake of fatty acids by the cell is not completely understood. Transport of fatty acids across the endothelial cells, the interstitial space, and the plasmalemma of the parenchymal cells is most likely a diffusion-like process (Van der Vusse et al., 1992). Recent experimental findings indicate that (1) specific membrane proteins are involved in transmembrane transport and (2) the uptake of fatty acids by brain is limited by the blood-brain barrier. 

The endothelial cells actively, as well as passively, serve to protect the brain. Because they contain a variety of drug-metabolizing enzyme systems similar to the drug-metabolizing enzymes found in the liver, the endothelial cells can metabolize neurotransmitters and toxic chemicals and, therefore, form an enzymatic barrier to entry of these potentially harmful substances into the brain. They actively pump hydrophobic molecules that diffuse into endothelial cells back into the blood (especially xenobiotics) with P-glycoproteins, which act as transmembranous, ATP-dependent efflux pumps. Although lipophilic substances, water, oxygen, and carbon dioxide can readily cross the blood-brain barrier by passive diffusion, other molecules depend on specific transport systems. Differential transporters on the luminal and abluminal endothelial membranes can transport compounds into, as well as out of, the brain. 

In the tissue cross-reactivity studies, the antibody has equal access to all tissues and all cell components (membrane, cytosol, nucleus) of the tissues on the section. This is not true in vivo where access to the tissues is governed by passive diffusion of the antibody to the tissue. Moreover, unless uptake by tissues is receptor-mediated, cell membranes preclude entrance of an antibody into the cells. In addition there are blood-brain, blood-nerve, blood-eye, and blood-testis barriers characterized by specialized endothelium that reduce movement of immunoglobulin into these protected spaces. Thus, some tissues have relatively little access by antibodies compared to others. Likewise, antigens within cells have little chance of access to the antibody compared to cell membrane or transmembrane antigens. 

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