The blood-brain barrier (BBB) tightly regulates transportation between the blood and brain to maintain homeostasis. It is formed by endothelial cells, pericytes, astrocytes, and a basement membrane. These structures comprise the neurovascular unit. Three barrier layers exist - the BBB, blood-cerebrospinal fluid barrier, and arachnoid epithelium. The BBB prevents diffusion of polar solutes through tight junctions between endothelial cells. It is selectively permeable to allow passage of water, oxygen, dioxide and lipid-soluble substances while restricting entry of toxins, bacteria, and macromolecules. The BBB physiology regulates glucose, amino acid, water and drug transport critical for brain function and protection.

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