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In addition, non-occludin adherens junctions are found intermingled with tight junctions. The integral membrane proteins of tight junctions are linked to the cytoskeleton via zone occluding-1 (ZO-1), ZO-2 and ZO-3. In contrast to occluding, claudins have been shown to be required for the formation of tight junctions. However, mice carrying the null mutation in the occludin gene develop morphologically normal tight junctions, indicating that occluding is not essential for proper tight junction formation. Occludin was the first integral membrane protein found to be exclusively localized within the tight junctions. The tight junctions between endothelial cells are responsible for the barrier function. Schematic illustration of junctional molecules. The "enzymatic blood-brain-barrier": Metabolic processes within the brain capillary endothelial cells are important to blood-brain function and control the entry of neurotransmitters into the brain.ġ1.2 Molecular Components of Tight Junctions.
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The large number of mitochondrias present in the brain endothelial cells provide energy for the function of this Na,K-ATPase.
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The continuous tight junctions that join the endothelial cells in the brain capillaries limit the diffusion of molecules across the BBB.It took an additional 70 years until Reese and colleagues localized the barrier to the capillary endothelial cells within the brain by electron-microscopic studies.īBB and the transport of molecules across the barrier. The term “blood-brain barrier” was coined, however, by Lewandowsky in 1898, after he and his colleagues had performed experiments to demonstrate that neurotoxic agents affected brain function only when directly injected into the brain but not when injected into the vascular system. In 1913, Edwin Goldman, an associate of Ehrlich, demonstrated the very same dyes, when directly injected into the cerebrospinal fluid (CSF), readily stained nervous tissue but not other tissues. He concluded that the dyes had a lower affinity for binding to the nervous system as compared to other tissues. trypan blue) stained all organs except the brain and the spinal cord. The discovery of the BBB dates back more than 100 years when, in the 1880s, Paul Ehrlich observed that intravenous administration of certain dyes (e.g. The endothelial cells forming the blood-brain barrier are highly specialized to allow precise control over the substances that enter or leave the brain.ĭiscovery of blood-brain barrier.
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Since many of these molecules regulate neuronal excitability, a similar change in the composition of interstitial fluid in the CNS can lead to uncontrolled brain activity. Elsewhere in the body the extracellular concentrations of hormones, amino acids and potassium undergo frequent fluctuations, especially after meals, exercise or stressful times. The blood-brain barrier (BBB) protects the neural tissue from variations in blood composition and toxins. 11.1 Blood-brain Barrier Maintains the Constancy of the Brain's Internal Environment