Benke-- 血脑屏障--2011-10-31

nullCerebrospinal fluid脑脊液 Cerebrospinal fluidnull成年人CSF总量约150ml； 脑积液的压力恒定。 nullCSF的产生部位、循环途径、生理功能产生部位：各脑室的脉络丛循环途径：生理功能：在脑、脊髓和颅腔、椎管之间形成缓冲。null脑脊液循环异常Blood-Brain BarrierBlood-Brain Barrier血脑屏障Outline Outline Where is the BBB located? What is the constituents of the BBB? What is the function of BBB? How to modulate the BBB in diseases? Can BBB be used as a therapeutic target?nullOutline Where is the BBB located? What is the constituents of the BBB? What is the function of BBB? How to modulate the BBB in diseases? Can BBB be used as a therapeutic target?null脑内的3个屏障Barriers are present at three main sites: the brain endothelium forming the blood–brain barrier (BBB) (1), the arachnoid epithelium (2) forming the middle layer of the meninges, and the choroid plexus epithelium (3), which secretes cerebrospinal fluid (CSF).nullOutline Where is the BBB located? What is the constituents of the BBB? What is the function of BBB? How to modulate the BBB in diseases? Can BBB be used as a therapeutic target?nullCellular constituents of the BBBTight junction A belt-like region of adhesion between adjacent cells. Tight junctions regulate paracellular flux, and contribute to the maintenance of cell polarity by stopping molecules from diffusing within the plane of the membrane.The barrier is formed by endothelial cells, surrounded by basal lamina and astrocytic perivascular endfeet.nullOutline Where is the BBB located? What is the constituents of the BBB? What is the function of BBB? How to modulate the BBB in diseases? Can BBB be used as a therapeutic target?Functions of the BBBFunctions of the BBB提供营养物质 维持脑组织间液（ISF）的稳态1、限制血液与ISF间的离子、液体流动； 2、分割中枢与外周两个神经递质库，阻止其交互作用； 3、为清除大分子及代谢产物提供通道。nullPathways across the blood–brain barriernullOutline Where is the BBB located? What is the constituents of the BBB? What is the function of BBB? How to modulate the BBB in diseases? Can BBB be used as a therapeutic target?nullBBB modulations under pathological conditions(1)bradykinin(缓激肽)acts on endothelial and astroglial bradykinin B2 receptors, leading to an increase in the [Ca2+ ]i and thus trigger the production of IL-6 through activation of NF-κB. (2) substance P, 5-HT and histamine acting on astrocytes can lead to the formation of ATP and prostaglandins (前列腺素), increasing endothelial permeability. (3) LPS leads to the release from microglia of TNFα, IL-1β and O2•–. All of which have the ability to open the BBB. (4) Astrocytes downregulate tPA production via TGFβ, leading to an influx of tPA from the blood. (5) AQP4 is upregulated on the astroglial endfeet, leading to astroglial swelling. nullOutline Where is the BBB located? What is the constituents of the BBB? What is the function of BBB? How to modulate the BBB in diseases? Can BBB be used as a therapeutic target?Targeting the BBB to flight diseaseTargeting the BBB to flight disease减小血脑屏障的渗透性： 增加血脑屏障的渗透性； 提高血脑屏障的保护作用。By increasing the tightness of the brain endothelial tight junctions； By upregulating BBB P-glycoprotein； By reducing the Ca2+ -mediated increase in BBB permeability.The neurovascular unitThe neurovascular unit血管神经单元nullNeurons Astrocytes Smooth muscle cells Endothelial cellsnullNeuronal activity regulates CBFHow to explain?nullPutative cellular mechanisms for the propagation of vasodilation from vessels in the activated site to resistance arteries upstreamnull