1c) The doors of the brain II: the choroid plexus, CSF and B-CSF barrier

true or false: Unlike the BBB, the vasculature in the choroid plexus contains sinusoid vessels.

false, the choroid plexus has fenestrated vessels because it needs access to blood/water to make CSF

Choroid plexus

- Entryway into brain - highly vascularized structure - contains the B-CSF barrier

stage 2 choroid plexi development

- columnar epithelium - apical nuclei - microvilli - sparse primary villi (tissue folds)

stage 4 choroid plexi development

- cuboidal epithelium - basal nuclei - microvilli - complex villi (multiple tissue folds)

stage 3 choroid plexi development

- cuboidal epithelium - central or apical nuclei - microvilli - more abundant primary villi (tissue folds)

stage 1 choroid plexi development

- pseudostratified - central nuclei - microvilli - no villi

What are the CSF flow generation hypotheses?

1) Beating cilia 2) Pulsations on vessels from heartbeat 3) Constant generation from one side and absorption on another 4) Combination of any of the above

Potential applications of glymphatic system

1) Gene therapy delivery 2) Drug targeting 3) Treatment for diseases related to molecule aggregates

what are the 3 functions of the choroid plexi?

1) Generate CSF 2) Form B-CSF barrier 3) Primary gateway of immune surveillance in the brain

What brain areas have permeable vessels?

1) Pituitary gland 2) "Vomiting center" 3) Circumventricular organs

What are the two plumbing systems in your body?

1) lymphatic system 2) glymphatic system

aquaporin deficient mice have similar pathology to patients of what disease?

Alzheimer's Disease

The main component of the neurovascular unit:

BMECs

Composed of two layers of the extracellular matrix, providing physical support to the barrier:

Basal membrane

what are conditions with high CSF volumes?

CP tumors, obstruction of destruction of arachnoid villi, obstruction of ventricular system

why is sleep important for the glymphatic system?

Glymphatic system is most active while you are asleep

what happens if CSF flow is interrupted?

Hydrocephalus, the brain will become damaged.

These cells transmit signals that act on the barrier, regulating its function:

Interneuron

What would be an explanation for why the Choroid plexus highly vascularized tissue?

It needs access to the blood to carry out its functions.

The CSF flows in what direction?

Lateral ventricles --> third ventricle --> fourth ventricle --> central canal

What is the CSF flow pathway?

Lateral ventricles → inter-ventricular foramina → third ventricle → cerebral aqueduct → fourth ventricle → central canal (into spinal cord) and median/lateral apertures (into subarachnoid spaces)

Contractile cells embedded in the basal membrane (extracellular matrix):

Pericytes

T or F: Each choroid plexus has same morphology and is organized into same structure in every ventricle.

TRUE

Why is the choroid plexus a primary site of immune cell entry?

The presence of fenestrated capillaries (not impermeable, can pass through)

how do immune cells enter the brain?

They cross the BCSFB/choroid plexus 1) migrate across the fenestrated vascular endothelium into the stromal space via signaling pathways 2) reactivation in perivascular space by APCs; move along the basal surface of the ependymal cells 3) cross the glia limitans into the CSF filled ventricle (either paracellularly or transcellularly).

why are the arachnoid villi important for maintaining balance?

They help brain tolerate small changes in pressure by absorbing more or less CSF depending on pressure needs

Main feature that makes the barrier impenetrable by sealing the space between cells:

Tight junctions

glymphatic system

a lymphatic system in the brain that participates in removal of wastes and the movement of nutrients and signaling compounds

Which of the following is the correct sequence of events for lymphocytes to cross into the brain's parenchyma? a. Cross the vascular endothelia, reactivation in perivascular space by APCs, cross the glia limitans. b. Activation by APCs in the bloodstream, cross the glia limitans, undergo apoptosis in the parenchyma. c. Cross the fenestrated endothelia, reactivation in the choroid plexus perivascular space, cross the ependymal epithelial monolayer. d. Activation by dendritic cells on the cervical lymph nodes, movement into lymph vessel, cross into the parenchyma.

a. Cross the vascular endothelia, reactivation in perivascular space by APCs, cross the glia limitans.

what type of cells form the glymphatic channels?

astrocytes (have aquaporins)

The presence of these cellular projections increases the TEER of the barrier (transendothelial electrical resistance):

astrocytic endfeet / astrocytes

where does reabsorption occur?

at the arachnoid villus

The CSF in the brain has both a unidirectional flow and a multidirectional flow. Which of the following correctly depicts the unidirectional flow? a. First ventricle > interventricular foramina > second ventricle > cerebral aqueduct > third ventricle > central canal (into spinal cord) b. lateral ventricles > interventricular foramina > third ventricle -> cerebral aqueduct > fourth ventricle > into the multidirectional flow c. lateral ventricles > cerebral aqueduct > third ventricle > interventricular foramina > fourth ventricle > median/lateral apertures (into subarachnoid spaces) d. First ventricle > second ventricle > third ventricle fourth ventricle > into the multidirectional flow

b. lateral ventricles > interventricular foramina > third ventricle -> cerebral aqueduct > fourth ventricle > into the multidirectional flow

why are the choroid plexi highly vascularized?

because it needs water to make CSF

why are the folds of the choroid plexi important?

because they increase the surface area and thus distributes blood to the ependymal cells

Which of the following is NOT a function of the CSF? a) Decreases the effective weight of the brain by ~90%. b) Cushions the brain and spinal cord from physical trauma, reducing the impact on the tissue. c) Allows gases into the brain parenchyma to ensure good oxygenation. d) Removes waste products from the CNS.

c) Allows gases into the brain parenchyma to ensure good oxygenation.

Which of the following is NOT a feature of the glymphatic system? a) Is driven by aquaporin channels on astrocytes b) It distributes nutrients in the parenchyma of the brain c) It is most active while awake d) It removes wastes such as amyloid plaques.

c) It is most active while awake

What is hydrocephalus? a. A condition that results when the normal flow of IF out of the brain is interrupted. b. A condition where the bones of the head are replaced by cartilage, resulting in a "water head." c. A condition that results when the normal flow of CSF is interrupted. d. A condition that results in an enlarged head due to an increased brain size.

c. A condition that results when the normal flow of CSF is interrupted.

congenital hydrocephalus

can go unnoticed for years; treatable with drainage tubes

Structure of choroid plexi

consists of a layer of cuboidal epithelial cells surrounding a core of capillaries and loose connective tissue *fenestrated capillaries, surrounded by ependymal cells

what are conditions with low CSF volumes?

dehydration, CSF leaks either due to trauma or medical intervention, atrophy or death of ependymal cells

What happens if you inject dye into CSF?

dye eventually crosses into brain (bypasses more permeable BCSFB)

What happens if you inject dye into the blood?

dye stays in the blood, will not cross into brain or CSF (due to impermeable BBB)

true or false: A defect in the volume of CSF will lead to disease regardless of the magnitude of the defect, as the brain has no ability to compensate.

false, the brain has the ability to compensate for smaller changes with reabsorption

true or false: The glymphatic system is a recently discovered waste clearance system specific to the spinal cord.

false, the glymphatic brain works inside of the brain and spinal cord

what kind of capillaries do the folds of the choroid plexi have?

fenestrated capillaries

what cells drive the glymphatic system?

glia (astrocytes)

how do immune cells migrate across fenestrated endothelium at the choroid plexus?

immune cells bind to signaling pathways/molecules → endothelial cells activated → open up

What is the BBB's permeability?

impermeable

The Choroid plexus plays an important role in the brain's immune system because

it is the entryway of immune cells into the ventricular space

The resident immune cells of the CNS:

microglia

what is the directional flow of CSF in the subarachnoid spaces?

multidirectional

where are the choroid plexi located?

one on each of the four ventricles

what immune cells are present in the parenchyma?

only microglia (NO T or B cells)

The choroid plexus resides in which meningeal layer?

pia mater (innermost layer)

reabsorption

process by which water and dissolved substances are taken back into the blood

what kind of immune cells are most of the microglia on the parenchyma?

resident effector microglia cells

What is the BCSFB's permeability?

selectively impermeable

What is the BMB's permeability?

selectively permeable

what is the brain's main source of CSF?

the choroid plexi

where do [non-microglial] immune cells survey the brain?

the choroid plexus/perivascular space, go in and out of BCSFB (check CSF)

what is the glymphatic system formed by?

the formation of the CSF and ISF (interstitial fluid) through channels inside the brain

where do microglia patrol?

the surface/meninges of the brain, in low numbers

true or false: the Choroid plexus is located within the ventricles and contains the B-CSFB.

true

what are examples of acquired hydrocephalus?

tumors, infections

what is the directional flow of CSF in the ventricular system?

unidirectional

acquired hydrocephalus

very serious, no room for expansion in the brain and needs surgery to treat the cause

congenital vs. acquired hydrocephalus

you are born with congenital, you develop acquired during your lifetime