CNS compartments

Question 1

Fluid barriers in the brain

Answer 1

Cell membrane: intracellular – interstitial fluid

Blood brain barrier: interstitial fluid – blood (not in all parts of the brain)

Blood – CSF barrier: CSF – blood (different barriers for ventricular CSF and blood and subdural CSF – blood)

CSF – interstitial barrier: (specialised parts of brain only)

Question 2

How is a stable extracellular environment controlled for neurons?

Answer 2

Blood brain barrier; production of interstitial fluid

Astrocytes; help maintain stable ionic composition and clearance of NT and other molecules/metabolites

Question 3

Blood brain barrier cells

Answer 3

Endothelia
Pericytes which cover endothelia
Astrocytes (neurovascular unit)

Question 4

Glia vessel interaction

Answer 4

Basal laminae of vessels and glial cell fuse, and the subpial layer of glial endfeet becomes continuous with the perivascular endfeet.

Question 5

Endothelial cells

Answer 5

Connected to each other via tight junctions (and adherens junctions): Claudins, Occludin, JAMs

High number of mitochondria, indicating high metabolic activity

Very few intracellular transport vesicles - suggestive of selective transport across endothelial cells.

Question 6

Pericytes

Answer 6

Contractile cell of blood vessel

Cover endothelial cells longitudinally 100%

Regulate blood flow, phagocytose debris, and influence permeability of endothelial cells

Question 7

Astrocytes

Answer 7

Central glial cells

Send “end feet” processes onto endothelia

Ensheathe entire abluminal side of blood vessel

Connect endothelia to neurons via joined basement membranes

Question 8

Microglia

Answer 8

Resident macrophages of CNS (Perivascular macrophages)

Constantly monitor their environment (“surveillance mode”). Control inflammation, destroy pathogens and clean up debris from dead or damaged cells

Maintain integrity of BBB: repair BBB breaches in integrity within minutes

Question 9

Ratio of pericyte to endothelial cells

Answer 9

1:3 ratio of pericyte to endothelial cell

Question 10

Movement of substances across the BBB is dependent on

Answer 10

Movement of substances across the BBB into the brain is directly proportional to their lipophilicity.

Very lipophilic molecules are much more permeating then less lipophilic molecules.

Question 11

Why are glucose and L-dopa very permeably across the BBB despite low lipid solubility?

Answer 11

Specific transporters

Question 12

Why are molecules like phenobarbital and phenytoin far less permeable than expected, given their lipophilicity?

Answer 12

Pumped out by ATP binding cassette transporters (ABCs). Usually in luminal membrane to pump molecules back into blood so mainly function as extruders

Protect brain from exogenous substances

Question 13

Mechanisms of substance movement across the BBB

Answer 13

Diffusion: gases diffuse along concentration gradients, O2 and CO2 dependent on blood flow. Other diffusion depends on lipid solubility and molecular mass.

Aquaporin channels: water

Transcytosis: receptor mediated and selective (transferrin, lipoproteins, IgG, insulin and leptin), absorptive and non selective (albumin).

Diapedesis: Mononuclear cells move through the cytoplasm of endothelial cells; under inflammatory conditions, they can use paracellular pathway

Transporters: glucose, AA, bases and nucleotides, T3, monocarboxylic acids, choline.

Question 14

What is the ventricular system?

Answer 14

A set of communicating cavities within the brain. These structures are responsible for the production, transport and removal of cerebrospinal fluid, which bathes the central nervous system.

Question 15

Role of CSF

Answer 15

Protection – acts as a cushion for the brain, limiting neural damage in cranial injuries.

Buoyancy – by being immersed in CSF, the net weight of the brain is reduced to approximately 25 grams. This prevents excessive pressure on the base of the brain.

Chemical stability – the CSF creates an environment to allow for proper functioning of the brain, e.g. maintaining low extracellular K+ for synaptic transmission.

Question 16

The choroid plexus

Answer 16

Strands of tightly coiled vascular tissue covered by an layer of cuboidal ependymal epithelial cells and called choroid plexus.

This is responsible for producing the cerebrospinal fluid.

Question 17

Choroid plexus histology

Answer 17

Strands of tightly coiled vascular tissue covered by an layer of cuboidal ependymal epithelial cells

Question 18

Where is most of the CSF made?

Answer 18

Cerebrospinal fluid is formed primarily by the choroid plexus of the lateral, third and fourth ventricles, with the largest contribution being made by the choroid plexus of the lateral ventricle.

Question 19

Where does drainage of the CSF occur?

Answer 19

In the subarachnoid cisterns (or space).

Question 20

What are subarachnoid cisterns?

Answer 20

Small projections of arachnoid mater (arachnoid granulations) protrude into the dura mater.

Question 21

Where does CSF drain from the subarachnoid cisterns?

Answer 21

They allow the fluid to drain into the dural venous sinuses.

Question 22

CSF passage through the ventricular system

Answer 22

The CSF passes from the choroid plexus via the interventricular foramen into the third ventricle, then posteriorly through the cerebral aqueduct into the fourth ventricle.

Question 23

How does the 4th ventricle communicate with the subarachnoid space?

Answer 23

The fourth ventricle communicates with the subarachnoid space through the median foramen of Magendie and the lateral foramina of Luschka.

Question 24

Two escape routes for CSF from subarachnoid space

Answer 24

Via arachnoid granulations into dural sinuses

Drainage along olfactory neural tracts through cribiform plate that extent into nasal mucosa and allow for CSF diffusion into nasal lymphatics (constantly runny nose may be sign of CSF rhinorrhea)

Question 25

Ependymal lining of ventricles histology

Answer 25

Ependymal lining of the ventricles is formed by a single layer of cells which may form a squamous, cuboidal or columnar epithelium, depending on their site within the ventricular system.

They are ciliated on their luminal surface and at their apical ends they are linked by gap junctions, with only occasional tight junctions.

Question 26

What barrier is present at the surface of the choroid tissues?

Answer 26

There is a blood CSF barrier present at the surface of the choroid plexus,

Question 27

Is there a barrier between the CSF and neural tissues?

Answer 27

No comparable barrier between the CSF and the neural tissues - interstitial fluid and CSF are fully permeable.

Question 28

Where do vessels supplying the brain lie?

Answer 28

Vessels supplying the brain lie in the subarachnoid spaces.

Question 29

CNS vessel basement membranes

Answer 29

Surrounded by their own basal lamina, and also carry with them the basal lamina that surrounds the CNS and is formed by the subpial glial cells.

Question 30

Space between vessel BM and glial BM contains

Answer 30

Continuous with subarachnoid space, exposed to CSF

Question 31

How are the two BMs different structurally in large and small vessels?

Answer 31

Large, space between both membranes, subarachnoid space filled with CSF

Small, basal laminae fuse, subpial layer of glial endfeet becomes continuous with the perivascular endfeet.

Question 32

Blood CSF barrier

Answer 32

Blood - CSF barrier is leaky compared with BBB

Question 33

What are the main components of the blood brain barrier?

Answer 33

Astrocytes, pericytes, endothelial cells with tight junctions (tightened with occludins)

Question 34

What is the relative potassium concentration of CSF compared to plasma?

Answer 34

Lower in CSF (Na+ and chloride are higher)

Question 35

Between which layers of meninges do you find CSF?

Answer 35

Between Arachnoid mater and Pia mater (in the subarachnoid space)

Question 36

How is CSF resorbed into the blood stream?

Answer 36

Via arachnoid granulations

Question 37

The majority of the CSF is formed by the choroid plexus in the

Answer 37

Lateral ventricles

Question 38

Each interventricular foramen connects the

Answer 38

Lateral ventricles and Third ventricle

Question 39

The concentration of protein in CSF compared to plasma is

Answer 39

Lower

Question 40

CSF leaves the ventricular system through apertures in the

Answer 40

Median (Foramen of Magendie) and lateral (Foramen of Luschka) aspects of the fourth ventricle