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Blood Brain Barrier

BLOOD BRAIN BARRIER AUTHORIZED MOLECULES ONLY The brain is shielded from potentially toxic substances by the presence of a barrier. The blood brain barrier (BBB) is an anatomical interface that separates the brain from the circulatory system. The endothelial cells of the blood vessels, perivascular cells (pericytes), astrocytes and neurons form the "neurovascular unit" and regulate effective functioning of the CNS. Astrocyte Astrocytic endfeet Blood vessel Pericytes BLOOD BRAIN SIDE SIDE TIGHT JUNCTIONS Tight junctions between endothelial cells essentially form the "barrier" that restricts transport of molecules between blood and brain interstitial fluid. In other words, the tight junctions confer a low paracellular permeability. ENDOTHELIAL CELLS The blood brain barrier is composed of a tigtly sealed monolayer of endothelial cells that line the blood vessels. This layer of endothelial cells normally precludes free exchanges of solutes between the blood and the brain. TRANSPORT ACROSS THE BLOOD BRAIN BARRIER How do molecules from the blood side reach the brain side? And vice versa? Small lipid-soluble molecules <400Da can cross the BBB via lipid-mediated diffusion. Carrier-Mediated Transporters, on both the blood and the brain side, facilitate transport of nutrients (like glucose), amino acids, nucleosides, vitamins and so on. lon Transporters like the sodium pump (Na*, K*-ATPase) on the brain side control Na* influx and K* efflux. They meet the energy demands of the BBB by ATP-dependent transport. Large proteins like leptin, insulin and immunoglobulin that are otherwise restricted from the barrier, use receptor-mediated transport systems to cross the BBB. BLOOD SIDE Impermeable drugs • Drugs designed for CNS disorders face the problem of being rejected by the blood brain barrier. Current strategies applied to enable these therapeutics to reach the brain are: - Design of small molecule drugs that cross the barrier by lipid-mediated diffusion. Trojan horse strategy - Conjugation with monoclonal antibodies against one of the BBB receptors (for example, insulin receptor) that act as surrogate ligands and cross the barrier. BRAIN SIDE Reference: Zlokovic BV. The blood-brain barrier in health and chronic neurodegenerative disorders. Neuron. 2008 Illustration by Anita Ramanathan

Blood Brain Barrier

shared by anitaram on May 01
The brain is shielded from potentially toxic substances by the presence of a barrier.


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