BLOOD BRAIN BARRIER ANATOMY

Paul Ehrlich

Who first injected a blue dye in the lumbar area which suggested the presence of a barrier protecting the brain parenchyma?

Edwin Goldmann

Who replicated Paul Ehrlich's experiment on rat's and sheep's brain?

Spinal cord and olfactory epithelium

According to Paul Ehrlich's initial experiment, what areas were stained blue after lumbar injection?

Brain parenchyma

According to Paul Ehrlich's initial experiment, what area was not stained blue after lumbar injection?

Spinal cord, optic vesicle, and olfactory vesicles

According to Edwin Goldmann's replication experiment, what areas were stained blue?

148 mEq/L

What is the approximate sodium (Na+) concentration in lumbar CSF?

136-145 mEq/L

What is the approximate sodium (Na+) concentration in blood?

2.9 mEq/L

What is the approximate potassium (K+) concentration in lumbar CSF?

3.5-5 mEq/L

What is the approximate potassium (K+) concentration in blood?

120-130 mEq/L

What is the approximate chloride (Cl-) concentration in lumbar CSF?

100-106 mEq/L

What is the approximate chloride (Cl-) concentration in blood?

50-75 mg/dL

What is the approximate glucose concentration in lumbar CSF?

70-100 mg/dL

What is the approximate glucose concentration in blood?

15-45 mg/dL

What is the approximate protein concentration in lumbar CSF?

6.8 x 10^3 mg/dL

What is the approximate protein concentration in blood?

7.3

What is the approximate pH of lumbar CSF?

7.4

What is the approximate pH of blood?

More acidic than blood

How does the pH of CSF compare to blood?

Low proteins

What is a characteristic of CSF composition due to the blood-brain barrier?

It does not allow transport of macromolecules

Why does CSF have low protein concentration?

Blood-Brain Barrier

What is located at the interface of the cerebral microvasculature and interstitial parenchyma?

Microvascular endothelial cells

What forms the Blood-Brain Barrier?

5000x more than Blood CSF barrier

How does the surface area of the Blood-Brain Barrier compare to the Blood-CSF Barrier?

Blood-CSF Barrier

What is located in the choroid plexus?

Epithelial cells

What forms the Blood-CSF Barrier?

Protection of brain parenchyma from blood-borne agents

What is a function of the Blood-Brain Barrier?

Maintenance of brain functioning and homeostasis

What is a function of the Blood-Brain Barrier?

Regulation of passage of substances

What is a function of the Blood-Brain Barrier?

Circumventricular Organs

What are parts of the brain lacking the BBB due to their secretory function?

Tanycytes

What do circumventricular organs have instead of tight junctions?

Fenestrations

Circumventricular organs have these, allowing some molecules to pass.

Neurohypophysis (Posterior pituitary)

Name a vascular brain structure around the ventricles that lacks the BBB.

Pineal gland

Name a vascular brain structure around the ventricles that lacks the BBB.

Median eminence

Name a vascular brain structure around the ventricles that lacks the BBB.

Area postrema (Vomiting center)

Name a vascular brain structure around the ventricles that lacks the BBB.

Subfornical organ

Name a vascular brain structure around the ventricles that lacks the BBB.

Subcommissural organ

Name a vascular brain structure around the ventricles that lacks the BBB.

Vascular organ (organum vasculosum) of the lamina terminalis

Name a vascular brain structure around the ventricles that lacks the BBB.

Vasopressin and oxytocin

What does the Neurohypophysis (Posterior pituitary) secrete?

Melatonin

What does the Pineal gland secrete?

Serves as barometer, Detects acidity of CSF

What are functions of the Median eminence?

Detects the levels of acidity in the body

What is a function of the Area postrema (Vomiting center)?

Functional unit of the central nervous system

What is the neurovascular unit?

Nephron

The neurovascular unit is similar in function to this structure in the renal system.

Five

How many components make up the neurovascular unit?

Brain capillary endothelial cells, Extracellular basal lamina, Pericytes, Astrocytes, Microglia

What are the five components of the neurovascular unit?

Present

Are enzymatic barriers present in cerebral capillary endothelial cells?

Mandatory

Is inductive influence from astrocytes mandatory for cerebral capillary endothelial cells?

Absent

Are fenestrations present in cerebral capillary endothelial cells?

Present

Are tight junctions present in cerebral capillary endothelial cells?

1500 Ω cm²

What is the transendothelial electrical resistance in cerebral capillary endothelial cells?

Low paracellular permeability

What does the high transendothelial electrical resistance in cerebral capillary endothelial cells indicate?

Minimal

What is the level of pinocytic vesicular transport in cerebral capillary endothelial cells?

Greater volume

How does the mitochondrial content of brain capillary endothelial cells compare to peripheral endothelial cells?

Luminal

What membrane are cerebral capillary endothelial cells exposed to flow on?

Present (e.g., amino acids)

Is established polarity-polarized transporters present in cerebral capillary endothelial cells?

Glucose, amino acids

What molecules undergo carrier-mediated transport in cerebral capillary endothelial cells?

Enzymatic barrier

What are some metabolic enzymes surrounding the BBB called that decarboxylate chemicals?

Transendothelial electrical resistance

What is brought about by endothelial cells and tight junctions, comparable to a frog's skin resistance to water?

Pinocytic vesicular transport

What is minimal in brain capillary endothelial cells, meaning they do not take in substances by engulfing?

Mitochondria

What is numerous in the capillary endothelium, mainly in the pericytes?

Brain capillary endothelial cells

What is the principal component of the blood-brain barrier?

Luminal surface of the blood vessel

What do endothelial cells continuously line?

Interconnected by a complex array of tight junctions

How are brain vascular endothelial cells different from peripheral endothelial cells?

Tight Junctions

What are responsible for generating transendothelial resistance and low paracellular permeability?

2000 Ohm-cm²

What is the transendothelial resistance value generated by tight junctions?

Low paracellular permeability

What is a characteristic of tight junctions regarding substance passage between cells?

Large molecules (>400 Da) or molecules with >8 H-bonds

What kinds of molecules cannot pass through the BBB because of tight junctions?

High selective transport of water-soluble compounds

What is the rationale behind this due to tight junctions?

Luminal area

Where are tight junctions seen?

Abluminal side

Where do adherens junctions occupy?

Blood vessel wall

What is the luminal side?

Brain or parenchymal or interstitial side

What is the abluminal side?

Three

How many principal transmembrane proteins compose tight junctions?

Claudins, Occludins, Junctional adhesion molecules (JAM)

What are the three principal transmembrane proteins of tight junctions?

Claudins

Which tight junction protein forms the backbone of tight junctional complexes?

22 kDa

What is the approximate molecular weight of Claudins?

Occludins

Which tight junction protein is recruited by claudins and regulates association with the cell membrane?

65 kDa

What is the approximate molecular weight of Occludins?

Multiple sclerosis

In what condition are Occludins pathologically involved?

Junctional adhesion molecules (JAM)

Which tight junction protein is located laterally to claudin and occludins and is responsible for junctional assembly?

Transmigration of inflammatory cells across barrier endothelial cells

What role do JAMs have?

Pericytes

What are cells that lie close to the endothelial cells of blood capillaries and small venules?

Around

What does the word "Peri" mean in Pericytes?

Contractile and seem to serve as a smooth muscle equivalent

What is a characteristic function of Pericytes in brain capillaries?

Tunica media or tunica adventitia

Pericytes serve as this in the brain parenchyma.

Blood flow regulator in the microvasculature

Pericytes are strong candidates for this role.

Regulates vascular permeability

What is a function of Pericytes?

Alters the radius of the cerebral vessel or musculature

What is a function of Pericytes?

Basal Lamina

Where do pericytes reside, forming an incomplete envelope?

Pericytes and endothelial cells

Which cells share the same extracellular basal lamina or basement membrane?

Type IV collagen, fibronectin, heparin sulfate, laminin, and entactin

What is the Basal Lamina mainly composed of?

Blood-brain barrier stability and angiogenesis

What is the Basal Lamina important for?

Astrocytes

What are the largest of the neuroglia?

Most numerous and most abundant cells in the CNS

How are Astrocytes described in terms of number?

Small round granules and glial filaments

What do Astrocytes contain?

Glial filament acidic protein

What are glial filaments in Astrocytes composed of?

Multiple ion transporters and channels

What do Astrocytes have?

Aquaporin-4

What do Astrocytes heavily express?

Glia limitans and Astrocytic foot processes

What are the two types of attachments for Astrocytic processes?