The blood brain barrier

1. BLOOD BRAIN
BARRIER
Neonatology4U
Dr Padmesh V
DNB (Ped), DM (Neonatology)

2. 1. Anatomy of the blood-brain barrier

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. • 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. • 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. • 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.

11. • 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.

12. • 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.

13. • 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.

14. 2. Development of blood-brain barrier

15. • 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.

16. 3. Physiology of the blood-brain barrier

17. • 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.

18. • 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.

19. • 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.

20. • 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

22. THANK YOU