Blood Brain Barrier presentation.pptVIP

Blood Brain Barrier: Structure, Function and Bypass by Microorganisms Presented by: Syeda Kashfi Qadri Discovery 1885: Paul Ehrlich: intravenous dyes in experimental organisms caused staining of all organs except the brain 1913: Edwin Goldmann put forward hypothesis that the cerebral capillaries provide anatomical basis for a physiological barrier between brain and the rest of the body 1950s: Electron microscopy demonstrated that the outermost layers of endothelial cells in brain capillaries are fused together What is the Blood Brain Barrier? Structural and functional barrier which impedes and regulates the influx of most compounds from blood to brain Formed by brain microvascular endothelial cells (BMEC), astrocyte end feet and pericytes Essential for normal function of CNS Regulates passage of molecules in and out of brain to maintain neural environment. Responsible for metabolic activities such as the metabolism of L-dopa to regulate its concentration in the brain. Structure of Blood Brain Barrier Differences between BMEC and normal endothelial cells Structural differences: Absence of fenestrations More extensive tight junctions (TJ) Functional differences: Impermeable to most substances Sparse pinocytic vesicular transport Increased expression of transport and carrier proteins: receptor mediated endocytosis No gap junctions, only tight junctions Limited paracellular and transcellular transport Integrity of BBB Tight Junctions Adherens Junctions Pericytes Astrocyte end feet Tight Junctions between BMEC Appear at sites of apparent fusion between outer leaflets of plasma membrane of endothelial cells Continuous Anastomosing Intramenbranous strands or fibrils on P face with complementary groove on E face Protein components: Claudin Occludin Junction Adhesion Molecules Accessory proteins Claudin 22kDa phosphoprotein 4 transmembrane domains localized in TJ strands Occludin 65kDa phosphoprotein, 1° structure very different from claudin Regulatory proteins: