Blood Brain Barrier

Blood Brain Barrier (BBB)

• a network of systems working in concert to keep damaging elements
  of the bloodstream out of the brain, while allowing certain substrates and controlled amount of glucose to exit the
  blood vessel. Large molecules, proteins and many ions are in very low concentration in the CSF when compared to
  blood plasma. It is a network that goes beyond the actual vascular structure

• There are interactions with special
  support cell (glial cell) called an astrocyte and a cell associated with blood vessels, an astrocyte

HIGHLIGHT

HE BLOOD-BRAIN BARRIER IS A CRITICAL ASPECT OF NEURONS AND BLOOD VESSELS ABILITY TO CO-EXIST. TO BE QUITE FRANK, BLOOD AND BRAIN HAVE AN UNEASY TRUCE. ALL THAT STANDS BETWEEN THE BLOOD AND TONS OF NEURONS BEING PUT TO THEIR SCREAMING DEATHS IS THE BLOOD-BRAIN BARRIER

Tight Junctions

where the cell membrane of adjacent cells are fused 360º, will not allow intercellular diffusion of blood elements. These tight junctions exist between endothelial cells of the blood vessels

Basal Lamina

in these arteries/capillaries is continuous. In many typical blood vessels, it is discontinuous

Pinocytotic

diffusion from taking place right through an endothelial cell

• In most tissues of the body, a high level of pinocytotic activity by endothelial cells transports solutes
  nonspecifically from the blood plasma to the perivascular space

• Not so with the CNS and the BBB!!! In fact, many
  drugs (especially those with large molecular weight
  or those that are NOT lipid soluble), cannot penetrate
  the BBB network

• For many solutes to get through the endothelium, they must be carried across in an active transport process.

Structure of the BBB

• restricts many large molecular weight molecules, most proteins and most microorganisms from entering the CNS

• It reduces glucose levels that reach the CNS. Glucose concentrations are, in general, lower within neural
  tissue compared to elsewhere in the body and are less variable throughout the day

• Many drugs, including antibiotics, have difficulty crossing the BBB

• Even blood borne neurtransmitters like epinepherine cannot enter the CNS,. Conversely, many CNS produced neurotransmitters cannot escape the confines of the “Hotel CNS”!

End Feet

astrocyctes have specialized structures which extend from the pial surface
(i.e. pia mater) to the arterial walls of central or cortical branches

• These end feet surround the vascular component, and may contribute to the relative impermeability of the
  vascular core

• That is why many include the astrocytic end feet as an integral part of the BBB complex

Pericytes

• specialized vascular support cells, possess multiple abilities including nutritive functions, hemolytic functions, phagocytic functions and embyonic induction of the vascular endothelium to form tight junctions

• It is the tight junction (and non-fenestrated) capillaries that make the BBB so unique in the human body

Cerebral Spinal Fluid

s free to diffuse through the ventricular wall (ependymal-glial membrane) into these chambers, as well.

• This is because there are no tight junctions between cells in this complex

• free to enter the extracellular compartments

Extracellular Fluid

diffuse from the honeycombs out into the sub-arachnoid space, through the pialglial membrane

• This is because there are no tight junctions between cells in this complex

• free to enter the sub-arachnoid space

Mixing CSF and ECF

• resulting mixing of the cerebrospinal
  fluid and extracellular fluid flow, in general, like
  a sink drain, from the ventricle wall to the sub-
  arachnoid space

• constant fluid flow aids in waste re-
  moval and serves as a substitute for lymphatic
  drainage (that does not exist in the CNS)

Metabolic Water

• Water produced by neuronal metabolism is also thrust into this mix
  and aids in removal of waste and non captured neurotransmitters

HIGHLIGHT 3

THE BLOOD BRAIN BARRIER IS NOT HOMOGENOUS THROUGHOUT THE CNS.

• THERE ARE REGIONS IN THE CNS THAT HAVE A MODIFIED BLOOD BRAIN BARRIER STRUCTURE. AND ITS A GOOD THING, BECAUSE THE CHOROID PLEXUS, A MODIFIED VASCULAR
  STRUCTURE FOUND IN INTERNAL CAVITIES CALLED THE VENTRICULAR SYSTEM IS RESPON SIBLE FOR PRODUCING THE LIFE-BLOOD (OR LACK THEREOF) OF NERVOUS TISSUE, CERE-
  BRAL SPINAL FLUID (CSF).

• BECAUSE IT IS DIFFERENT FROM THE REGULAR BLOOD-BRAIN BARRIER, THE RELATIONSHIP BETWEEN THE CHOROID PLEXUS AND THE CSF IT SECRETES IS
  CALLED THE BLOOD-CSF BARRIER

HIGHLIGHT 4

THE CHOROID PLEXUS IS ANOTHER VASCULAR COMPLEX, DISTRIBUTED
THROUGHOUT THE VENTRICULAR SYSTEM OF THE HUMAN BRAIN. IT PRODUCES ABOUT 500-550 ML OF CSF IN 24 HOURS. THERE IS COMPLETE TURNOVER 3-4 TIMES IN A DAY

Vascular Structure

• The vascular element has a folded, ribbon-like structure, with numerous villa

• at the core encased by dense connective tissue and capped by epithelial cells called choroid cells

• The choroid cells have tight junctions between them. This is the predominant feature of the blood CSF barrier

Choroid Plexi

are found throughout the ventricular system, typically (with one MAJOR exception) lining the floor of each cavity

• the capillary beds are fenestrated, allowing a significantly less restriction to intracellular transport of materials into the connective tissue surrounding them

• Tight junctions are NOT between endothelial cells, so intercellular transport is much less restricted

• So, the presence of tight junctions between the choroid epithelial cells is critical to the “tightness” of the bar-
  rier function

In most all cases, the CSF levels of certain solutes are similar found within actual neural tissue (i.e. cerebral cortex)

• Again, glucose, proteins, albumin and ions such as calcium and potassium are lower concentration in CSF
  compared to blood plasma.

• Cl Mg and Na are higher concentration in CSF compared to blood plasma.

• Blood-circulating neurotransmitters/neuroactive agents (like epinephrine and nor-epinephrine) cannot cross
  the blood brain barrier AND VICE VERSA!

Any shift in the relative concentrations of ions, glucose, neurotransmitter metabolites and or blood proteins maybe indicative of disease processes

• Low glucose levels in conjunction with elevated neutrophils count in the CSF: bacterial meningitis

• Red blood cells in the CSF: hemorrhage in the sub-dural space

• Lymphocytes (as few as 50 cells/ml) in the CSF may indicate multiple sclerosis