CSF Secretion and BBB

Question 1

What are the three major cell layers of the choroid plexus?

Answer 1

Choroid epithelium - outermost, forms tight barrier

Supporting layer - middle layer, no direct role in secretion

Endothelium of choroid plexus capillaries - inner most, thin with fenestrations between the edges of individual cells

Question 2

How can small molecules (ions, glucose, water) move from the plasma into the spaces inside the choroid plexus villi?

Answer 2

Diffusion through the endothelial cell membranes

Diffusion through the fenestrations

Pinocytosis

*Movement of large molecules is limited/prevented

Question 3

What is the function of the tight junctions of the choroid plexus epithelium?

Answer 3

Formation of the Blood-CSF barrier

Lipid soluble compounds can diffuse directly through, but water and water soluble compounds can only occur through membrane transport proteins

Question 4

Describe the structure of the basolateral and apical membranes

Answer 4

Basolateral surface contains interdigitations

Apical surface contains tight junctions and microvilli

Both of these increase surface are available for transport

Question 5

Describe the function of the basolateral and apical membranes

Answer 5

Contain different transport proteins

Mediate the transport of ions, water, and other small molecules

Question 6

What is the location and function of NA/K ATPase?

Answer 6

Apical membrane

Export of sodium into the ventricle

Question 7

What is the major purpose of transport mechanisms on the basolateral membrane?

Answer 7

Critical for maintaining intracellular concentrations of ions which are transported across the apical membrane

Question 8

What is the location and function of carbonic anhydrase?

Answer 8

Within the epithelial cells

Catalyzes the formation of HCO3 and H+ from water and CO2

Critical for maintaining intracellular ions which are involved in membrane transport and pH regulation

Direct role in CSF secretion

Question 9

What are the major monovalent ions of the CSF and the importance of their transport across the basolateral and apical membranes?

Answer 9

Na and Cl

Net movement of these ions into the ventricles raises the osmotic pressure within the ventricles driving osmosis

Question 10

What are the most clinically useful drugs for reducing the rate of CSF secreiton?

Answer 10

Carbonic Anhydrase inhibitors

Topiramate, acetazolamide

Question 11

How does CSF mix with ISF surrounding neurons and glial cells?

Answer 11

Diffusion through the intercellular spaces of the ependymal cell layer

This free exchange is possible becuase tight junctions are not formed between the cells of ependymal and pial layers

Question 12

Aside from the choroid plexus, what produces CSF?

Answer 12

CNS capillary endothelial cells

The tight junctions between these cells are responsible for the creation of the blood brain barrier

Question 13

What is responsible for inducing the structural and functional specializations of the CNS capillary endothelial cells?

Answer 13

Astrocytes

Question 14

What is one drawback to the blood-brain and blood-CSF barriers?

Answer 14

The can prevent entry into the CNS of many therapeutically useful compounds

Question 15

What is vasogenic edema?

Answer 15

Disorder of fluid balance caused by disruption of the blood-brain barrier

Question 16

What causes vasogenic edema?

Answer 16

Plasma proteisn leak into the CNS, increasing the osmotic pressure of the ISF and drawing water into the interstitial space

This increase in brain ISF compresses blood vessels in the brain

Can also exert pressure and cause herniation

Question 17

What injuries can result in vasogenic edema?

Answer 17

Head injury, hemorrhage, infarct, tumor, inflammation of infection

Question 18

What is osmotic edema?

Answer 18

Plasma osmolarity is reduced below normal, causing water to move into the CNS

Can be caused by hyponatremia and excessive consumption of water or hypotonic IV fluids

Question 19

What is hydrostatic edema?

Answer 19

Hydrostatic pressure forces fluid from the plasma across the BBB into the CNS

May result from malignant hypertension

Question 20

What is interstitial edema?

Answer 20

Fluid imbalance between the CSF filling the ventricles and the surrounding brain

E.g. non-communicating hydrocephalus causes interstitial edema