血脑屏障相关知识课件.ppt

blood-brain barrier(BBB)Hua fuQ:279486524 Key functions of the BBB Discovery of the blood-brain barrier Anatomy of the blood-brain barrier Circumventricular organs Factors that can lower the blood-brain barrier Blood-brain border and Glucose Blood-brain barrier permeability in the mouse brain Outline Outline Key functions of the BBB A mechanism that controls the passage of substances from the blood into the cerobrospinal fluid and thus into the brain and spinal cord.The blood-brain barrier(BBB)lets essential metabolites,such as oxygen and glucose,pass from the blood to the brain and central nervous system(CNS)but blocks most molecules that are more massive than about 500 daltons.This is a low mass in biomolecular terms and means that everything from hormones and neurotransmitters to viruses and bacteria are refused access to the brain by the BBB.It also means that many drugs,which would otherwise be capable of treating disorders of the CNS,are denied access to the very regions where they would be affective.Key functions of the BBB are:Protecting the brain from foreign substances(such as viruses and bacteria)in the blood that could injure the brain Shielding the brain from hormones and neurotransmitters in the rest of the body Maintaining a constant environment(homeostasis)for the brain Discovery of the blood-brain barrierThe special properties of the blood-brain barrier were first observed in the late 19th century by the German bacteriologist Paul Ehrlich.He found that when he injected colored dyes into the blood stream they leaked out of capillaries in most regions of the body to stain the surrounding tissues;the brain,however,remained unstained.Ehrlich wrongly surmised that the brain had a low affinity for the dyes.It was his student,Edwin Goldman,who did the other half of the experiment and realized the truth of what was going on.Goldman injected a dye into the cerebrospinal fluid that surrounds the brain and observed that it stained the brain,but nothing else.Goldmann correctly concluded that the dye was unable to cross the specialized walls of brain capillaries.Anatomy of the blood-brain barrierDiagram of the blood-brain barrier transverse to a capillary(A)Diagram of a brain capillary in cross section and reconstructed views,showing endothelial tight junctions and the investment of the capillary by astrocytic end feet.(B)Electron micrograph of boxed area in(A),showing the appearance of tight junctions between neighboring endothelial cells(arrows).(A after Goldstein,Goldstein and Betz,1986;B from Peters et al.,1991.)Anatomy of the blood-brain barrierCircumventricular organs The circumventricular organs are regions of the brain where the blood-barrier barrier is weak.These regions allows substances to cross into brain tissue more freely and thereby allow the brain to monitor the makeup of the blood.Various factors and conditions can lead to a lowering of the BBB.These include:Hypertension(high blood pressure)Hyperosmolitity(a high concentration of a substance in the blood)Microwaves Radiation Infection Injury to the brain due to trauma,ischemia,inflammation,or pressure Additionally,the BBB is not fully formed at birth.Factors that can lower the blood-brain barrier Blood-brain border and GlucoseTo metabolize glucose in the brain,or to perform cerebral glucose metabolism,requires a complex,multi-step process in which the sugar is transported into the brain-breaking the well walled blood-brain border,converted to another substance,completes a set of chemical reactions,and then ultimately oxidized to carbon dioxide and water for the full use of it as energy.Blood-brain barrier Blood-brain barrier permeability in the mouse brainMasaki Ueno.Acta Neuropathol(2004)107:532538Blood-brain barrier permeability in the rat brainFig.2AF Light microscopic photographs showing the staining for HRP with TMB in WKY(A and D),SHR(B and E),and SHRSP(C and F).D,E,and F are higher-power magnifications ofthe staining for HRP with TMB in the hippocampal area indicated by arrows in A,B,and C,respectively.No HRP staining is observed in the hippocampus and cortex of WKY(A and D).The staining for HRP is seen in the hippocampus,especially around vessels(E,F:arrows)along the hippocampal fissure of SHR(B and E)and SHRSP(C and F).Scale bars indicate 1mmMasaki Ueno.Acta Neuropathol(2004)107:532538Nicolas.American Journal of Hypertension,2010 Thank a lot!