Question 3. Based on your reading \"Blood Brain Barrier\" As the name implies, t

Question

Question 3. Based on your reading "Blood Brain Barrier" As the name implies, the blood-brain-barrier is a structure that tries to separate the blood flow from the brain. (I) Why is that; (II) what are the anatomical structures (i.e., the cells, fibers, tissues) that are responsible for establishing the blood -brain-barrier (III) for what type of chemicals is the blood-brain-barrier not much of an obstacle; and (IV) based on your Reading, what new developments have helped to get drugs delivered across the blood-brain-barrier? (10 pts)

Explanation / Answer

1)Blood- brain- barrier is essential for maintaining homeostasis in the Central nervous system and proper functioning of neurons.It does so by regulating the movement of ions, cells and molecules from blood into brain. This barrier also prevents the entry of pathogens and toxins via blood stream to the brain tissue. Destruction of this barrier is a pathological conditions which can be observed in different neurological diseases.

2) Blood vessels are made up of endothelial cells. These cells line the wall of blood vessels. Endothelial cells in brain capillaries are tightly apposed by tight junctions.

Pericytes are embedded in the basement membrane, and cover about 1/3 of the surface of capillaries .Astrocytes support capillaries with their foot processes.

Tight junctions are multi molecular complexes consisting of transmembrane and cytoplasmic protein associated with membrane. They prevent the paracellular transport of certain molecules.

Transmembrane protein include occludins, claudins and JAMs. cytoplasmic proteins include zonula occludens (ZO). ZO proteins contains PDZ domains with which they associate with the C terminal domain of claudins. To occludins they associate via GUK domains and another PDZ domains mediates interaction of ZO proteins with JAMs.

3) Factors which determine the movement of molecules across Blood brain barrier are charge, molecular weight,lipid solubility, and surface activity. Low molecular weight and lipophilic molecules can cross blood brain barrier via transmembrane diffusion. Although highly liphophilic molecules can become trapped in the capillary bed, unable to reach the brain cells.

4) drug delivery through transporter in blood brain barrier : normally amino acids cross blood brain barrier via active transporters. Drugs can be linked to amino acids to get them delivered to the brain cells. Prodrug of dopamine linked with three amino acid has been synthesized to increase its uptake

enhancers of brain permeability : transient disruption of blood brain barrier by decreasing expression of tight junctions proteins can allow chemotherapeutics agents to reach the brain. One such molecule is cereport.

Nanoparticles: Non viral nanoparticles are small sized particles which can carry drugs molecules. They have been shown to increase drug concentration in brain. This feature can be attributed to their small size which allows them to cross the blood brain barrier. other reason could be drug's increased circulation time in blood, increasing its chances of crossing the barrier.

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