CNS compartments Flashcards
Fluid barriers in the brain
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)
How is a stable extracellular environment controlled for neurons?
Blood brain barrier; production of interstitial fluid
Astrocytes; help maintain stable ionic composition and clearance of NT and other molecules/metabolites
Blood brain barrier cells
Endothelia
Pericytes which cover endothelia
Astrocytes (neurovascular unit)
Glia vessel interaction
Basal laminae of vessels and glial cell fuse, and the subpial layer of glial endfeet becomes continuous with the perivascular endfeet.
Endothelial cells
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.
Pericytes
Contractile cell of blood vessel
Cover endothelial cells longitudinally 100%
Regulate blood flow, phagocytose debris, and influence permeability of endothelial cells
Astrocytes
Central glial cells
Send “end feet” processes onto endothelia
Ensheathe entire abluminal side of blood vessel
Connect endothelia to neurons via joined basement membranes
Microglia
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
Ratio of pericyte to endothelial cells
1:3 ratio of pericyte to endothelial cell
Movement of substances across the BBB is dependent on
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.
Why are glucose and L-dopa very permeably across the BBB despite low lipid solubility?
Specific transporters
Why are molecules like phenobarbital and phenytoin far less permeable than expected, given their lipophilicity?
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
Mechanisms of substance movement across the BBB
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.
What is the ventricular system?
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.
Role of CSF
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.
The choroid plexus
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.
Choroid plexus histology
Strands of tightly coiled vascular tissue covered by an layer of cuboidal ependymal epithelial cells
Where is most of the CSF made?
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.
Where does drainage of the CSF occur?
In the subarachnoid cisterns (or space).
What are subarachnoid cisterns?
Small projections of arachnoid mater (arachnoid granulations) protrude into the dura mater.
Where does CSF drain from the subarachnoid cisterns?
They allow the fluid to drain into the dural venous sinuses.
CSF passage through the ventricular system
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.
How does the 4th ventricle communicate with the subarachnoid space?
The fourth ventricle communicates with the subarachnoid space through the median foramen of Magendie and the lateral foramina of Luschka.
Two escape routes for CSF from subarachnoid space
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)
Ependymal lining of ventricles histology
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.
What barrier is present at the surface of the choroid tissues?
There is a blood CSF barrier present at the surface of the choroid plexus,
Is there a barrier between the CSF and neural tissues?
No comparable barrier between the CSF and the neural tissues - interstitial fluid and CSF are fully permeable.
Where do vessels supplying the brain lie?
Vessels supplying the brain lie in the subarachnoid spaces.
CNS vessel basement membranes
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.
Space between vessel BM and glial BM contains
Continuous with subarachnoid space, exposed to CSF
How are the two BMs different structurally in large and small vessels?
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.
Blood CSF barrier
Blood - CSF barrier is leaky compared with BBB
What are the main components of the blood brain barrier?
Astrocytes, pericytes, endothelial cells with tight junctions (tightened with occludins)
What is the relative potassium concentration of CSF compared to plasma?
Lower in CSF (Na+ and chloride are higher)
Between which layers of meninges do you find CSF?
Between Arachnoid mater and Pia mater (in the subarachnoid space)
How is CSF resorbed into the blood stream?
Via arachnoid granulations
The majority of the CSF is formed by the choroid plexus in the
Lateral ventricles
Each interventricular foramen connects the
Lateral ventricles and Third ventricle
The concentration of protein in CSF compared to plasma is
Lower
CSF leaves the ventricular system through apertures in the
Median (Foramen of Magendie) and lateral (Foramen of Luschka) aspects of the fourth ventricle
