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Blood Brain Barrier by Dr Padmesh V

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The blood brain barrier

Publicado en: Salud y medicina
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Blood Brain Barrier by Dr Padmesh V

  1. 1. BLOOD BRAIN BARRIER Neonatology4U Dr Padmesh V DNB (Ped), DM (Neonatology)
  2. 2. 1. Anatomy of the blood-brain barrier
  3. 3. • INTRODUCTION: • To maintain normal brain function, the neural environment must be preserved within a narrow homeostatic range. • This requires a tight regulation of transportation of cells, molecules and ions between the blood and the brain. • Such tight regulation is maintained by a unique anatomical and physiological barrier, formed collectively in the central nervous system (CNS).
  4. 4. • The Neuro-Vascular Unit: • The term blood–brain-barrier has a long history, but it does not adequately encompass the wide range of morphological features and functional characteristics. • For this reason the term “neuro vascular unit” (Neuwelt,2004) is being increasingly used. • It comprises: pb Gate – Endothelial cells, – Pericytes, – Microglia, – Astrocytes, and – Basement membrane – Tight junction
  5. 5. • Three barrier layers contribute to the separation of the blood and neural tissues: • (1) a highly specialized endothelial cells (EC) layer comprising the blood-brain barrier (BBB) and partitioning the blood and brain interstitial fluid, • (2) The blood-CSF barrier (BCSFB) with the choroid plexus epithelium which secretes the specialized cerebral spinal fluid (CSF), and • (3) The arachnoid epithelium separating the blood from the subarachnoid CSF.
  6. 6. • The BBB components include: pb gate • Endothelial cell layer • Basement membrane • The endothelium is surrounded by : –Pericytes –Astroglial foot processes Adjoined by tight cell-to-cell junction proteins and pinocytic vesicles. Form an additional continuous stratum that separates blood vessels from brain tissue.
  7. 7. • Endothelial Cell layer lining brain capillaries, exhibits a greater number and volume of mitochondria, augmenting the selective molecular permeability of the BBB. • The basement membrane encompasses pericytes and endothelial cells and is closely adjacent to the plasma membranes of astrocyte end-feet, enclosing the cerebral capillaries . • Transmembrane proteins (junctional adhesion molecule-1, occludin, and claudins 1/3, 5, and possibly 12) and Cytoplasmic accessory proteins (zonula occludens-1 and -2, cingulin, AF-6, and 7H6) establish the tight junctions between adjacent endothelial cells.
  8. 8. • Junctional adhesion molecules maintain tight junction properties. • Claudins facilitate tight barrier capabilities, • Occludins and Zonula occludens-1 regulate targeted signaling. • Pericytes are enveloping brain microvessels and capillaries and are found in close proximity to astrocytes and neurons. • Pericytes play a critical role in the formation and maturation of the BBB. • Pericytes control cerebral blood flow by regulation of capillary diameter through actin fibers in the pericytic cell body.
  9. 9. • Astrocytes interact with pericytes and microvascular endothelial cells by endfeet protrusions ensheathing the capillaries. • Interactions may also exist with smooth muscle cells at arterioles. • Astrocytes play important roles in maintenance of BBB, in homeostasis of extracellular concentration of transmitters, metabolites, ions and water. • Also serve as stem cells during development. • Interaction between astrocytes and neurons determine synaptic transmission.
  10. 10. 2. Development of blood-brain barrier
  11. 11. • An early feature of BBB development is the formation of tight junctions. • In humans, a brain of a 14 week fetus express occludin and claudin-5 in the capillary endothelium. • Human post-mortem studies of perinatal deaths and stillborn fetuses have demonstrated that a barrier to trypan blue exist from at least the beginning of the second trimester. • Culture studies suggest that astrocytes have a key role in regulating the tightness of the BBB. • BBB matures during fetal life & is well formed by birth.
  12. 12. 3. Physiology of the blood-brain barrier
  13. 13. • Each of the three main CNS interface layers: – BBB, – Choroid plexus epithelium and – Epithelium of the arachnoid mater, • Tight junctions between adjacent cells restrict diffusion of polar solutes through intercellular cleft (paracellular pathway). • The barriers are permeable to O2 and CO2 and other gaseous molecules such as helium, xenon and many gaseous anesthetics. • Lipid soluble substances can pass the barrier by diffusion. • Principally, the BBB is also permeable to water, however solute carriers on the apical and basal membranes together with ectoenzymes and endoenzymes regulate small solute entry and efflux. functions as a physical, transport, metabolic, and immunologic barrier.
  14. 14. • Transfer of some molecules is regulated by multidrug transporters that can limit their concentrations within the central nervous system. • Aquaporins: – Water homeostasis. – Aquaporin 1 (AQP1) detected on epithelial cells in the choroid plexus whereas AQP4, AQP5 and AQP9 are localized on astrocytes and ependymal cells.
  15. 15. • 1. Transport of glucose and amino acids: • Endothelial cells of the brain microvasculature, astrocytes, and the choroid plexus express the insulin independent glucose transporter GLUT1. • GLUT1 plays a vital role in brain glucose uptake and is highly expressed in cells forming the blood-tissue barriers and in astrocytes. • Another important aspect is brain protection against neuroactive substances such as aspartate and glutamate. • The BBB is largely impermeable to these amino acids.
  16. 16. • 2. Transport of macromolecules- Proteins and Peptides • Most aminoacids are neutral and large, thus incapable of passive diffusion to the brain. • Endocytic vesicles account for the main delivery of large molecular weight substances such as proteins and peptides, through the BBB. • Protein synthesis in the brain is dependent upon the supply of essential amino acids. • 3. Drug delivery • Penetration of large molecules from the blood into the brain is prevented by the BBB
  17. 17. THANK YOU