Blood Brain Barrier

  • Created by: LBCW0502
  • Created on: 02-10-18 19:26
Outline the discovery of the BBB by Erhlich
Erhlich injected Trypan Blue dye into a rat and observed that the PNS was stained but the CNS was unstained and concluded that the CNS had a different affinity for the dye (disapproved)
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Outline the discovery of the BBB by E.Goldmann
Goldmann modified Erhlich's experiment. First experiment - injected Trypan Blue dye into the PNS (PNS stained, CNS unstained). Second experiment - injected Trypan Blue dye into CNS (CNS stained, PNS unstained). Conclusion - there was a BBB present
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What did the electron microscopy of brain capillaries confirm about the anatomical basis of the BBB?
The brain capillaries are at the same level as the BBB (electron microscopy used plus macromolecular tracers such as horseradish peroxidase)
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Outline the anatomy of the vascular supply of the brain
Carotid arteries, vertebral arteries. Circle of Willis. Sub-divisions to form: pial arteries (pial - covering layer of brain), penetrating arteries, penetrating arterioles, intracerebral arterioles, capillaries
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What can be concluded from the India ink study about brain capillaries?
Brain capillaries are very complex
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What can be concluded from the scanning electron micrograph of brain capillaries?
Brain capillaries are very dense
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Describe the structures around the lumen of the BBB
Capillary lumen surrounded by endothelium (one cell thick). Surrounded by astrocytes, pericytes. Endothelium is on top of basement membrane, Tight junctions, paracellular cleft
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What are the components of the neurovascular unit?
Basement membrane, astrocyte endfoot, tight junction, pericyte, endothelial cell, neuron, oligodendrocyte, astrocyte and microglia
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What is the function of microglia?
Act as macrophages and are involved in phagocytosis
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What does glial fibrillary acidic protein (GFAP) show?
Structure of astrocyte which long projections and the lumen with the astrocytic endfeet
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Describe the structure of astrocytic endfeet and capillary endothelium
Astrocytic end feet form rosette like structures. One endothelial cell refers end feet from more than one astrocyte. An astrocyte can have two end feet which interact with more than one endothelial cell
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What are the functions of astrocytes?
Energy and nutrient support of neurons. Ion and water homeostasis. Termination of synaptic activity. Maintenance of BBB. Breathing regulation
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What are the different permeation mechanisms (4)
Simple diffusion, passive diffusion, transporters (influx/efflux), endocytosis
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What does the intercellular junctional complex consist of?
Adherens junctions (in all cells and doesn't interfere with cell movement) and tight junctions (no cell movement)
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Which proteins are in the tight junction?
Claudin, Occludin, JAMs, ESAM
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Which proteins are in the adherens junction
PECAM, VE-cadherin, alpha/beta/gamma catenin
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What are the features of the cerebral capillary endothelium?
Physical barrier, continuous strands of tight junctions. Trans-endothermal electrical resistance is very high (>1000). High levels of transporters, reduced number of vesicles/fenestrations. Metabolic barrier/enzyme systems
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What do lipid bilayers consist of?
Phospholipids - hydrophilic head and hydrophobic tail (simple diffusion for small molecules e.g. ethanol)
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Describe features of the experiment for morphine, codeine and heroin
Morphine is hydrophilic (not much can pass BBB), codeine (with CH3 group) is more lipophilic and can pass BBB. Heroin is very lipophilic and passes BBB rapidly (metabolised in brain to form morphine with cannot leave BBB - long lasting effects)
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Why can D-glucose pass the BBB despite being hydrophilic?
Glucose passes the BBB using a GLUT1 transporter (also able to transport different amino acids)
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What are the two types of transport proteins?
Facilitated diffusion transporters (down concentration gradient) and secondary active transporters (against concentration gradient and uses ATP) - specific to substrate
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How does cyclosporin A pass the BBB
Using an ABC transporter (active efflux mechanisms)
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Describe the structure of P-glycoprotein
Helical structure with two units (ATP)
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What are the three subtypes of ABC?
P-glycoprotein, breast cancer resistance protein, multi drug resistance associated protein
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What are the two types of endocytosis processes?
Fluid phase endocytosis and selective endocytosis
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What are the functions of the BBB
Controls molecule influx into brain ISF, supplies brain with essential nutrients, mediates efflux of waste products, restricts ionic/fluid movements, protects brain from fluctuations in ionic plasma composition, provides brain with stable ISF
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What does the blood-CSF barrier consist of?
Chorois plexus and arachnoid membrane
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What are the functions of choroid plexuses?
Produced CSF, synthesises polypeptides, contributes to regulating brain ISF (electrical resistance)
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Which ions are involved in CSF secretion?
Na, K, Cl, HCO3, H
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Describe the volumes and fluid production rates in CSF and ISF
More ISF in brain. Higher fluid production rate in CSF compared to ISF
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Describe the pathophysiology of the BBB
E.g. Alzheimer's disease toxin due to high concentration of amyloid beta (involved LRP-1)
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Other cards in this set

Card 2

Front

Outline the discovery of the BBB by E.Goldmann

Back

Goldmann modified Erhlich's experiment. First experiment - injected Trypan Blue dye into the PNS (PNS stained, CNS unstained). Second experiment - injected Trypan Blue dye into CNS (CNS stained, PNS unstained). Conclusion - there was a BBB present

Card 3

Front

What did the electron microscopy of brain capillaries confirm about the anatomical basis of the BBB?

Back

Preview of the front of card 3

Card 4

Front

Outline the anatomy of the vascular supply of the brain

Back

Preview of the front of card 4

Card 5

Front

What can be concluded from the India ink study about brain capillaries?

Back

Preview of the front of card 5
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