CNS compartments e.g.BBB Flashcards Preview

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Flashcards in CNS compartments e.g.BBB Deck (29):

Fluid barriers in brain (4)

Cell membrane (intercellular - interstitial fluid)
BBB (interstitial fluid - blood)
Blood CSF barrier
CSF interstitial barrier


What is BBB between

Lumen of cerebral blood vessels and brain parenchyma


What is role of BBB

Homeostasis of internal environment of brain --> regulates ionic composition of interstitial fluid --> allows molecules needed for brain function through but not harmful substances
Makes interstitial fluid


Role of endothelial cells in BBB

Barrier forming cells with no fenestrations linked by luminal tight junctions --> restrict intercellular ion flow.
High number of mitochondria and few intracellular vesicles --> active and selective transport across cells


What are the roles of pericytes covering endothelial cells in BBB

Regulate blood flow by contraction/relaxing, phagocytose debris and influence permeability of endothelial cells.
Maturation of pericyte and endothelial cell interlinked


What is the role of astrocytes in BBB

Extend endfeet which ensheath abluminal side of blood vessel --> contain aquaporin and K+ channel to facilitate interstitial solute clearance. --> help maintain stable ionic composition and clearance of metabolites/NTs
Induce BBB properties in endothelial cells e.g. TJs and connect endothelia indirectly to neurones


What is neurovascular coupling in context of BBB why is it important

Neurones connected to cells of BBB either indirectly or directly --> neurovascular coupling allows regulation of blood flow in response to neuronal demand


How is BBB selectively permeable

Diffusion of substances depends on molecular mass, hydration radius, lipid solubility and interaction with plasma proteins


What sort of molecules can diffuse across BBB

Small e.g. oxygen, Co2 lipophilic


What transport mechanism can increase permeability

Aquaporins --> H20 permeability
Transcytosis for macromolecules: receptor mediated e.g. lipoprotein, IgG, insulin or absorptive (non selective) e.g. albumin
Diapedesis: PMNs move through cytoplasm or paracellularly as TJ break down in inflammation
Selective transporters (facilitated diffusion and active transport): solute transporters SLCs, GLUT1, AAs


What mechanisms decrease permeability

Transporters extrude substances e.g. ABCs
Endocytosis (endosomes fuse with lysozyme --> degradation)
Import followed by enzymatic conversion e.g. dopamine
Enzymatic conversion out of cell


What is significance/relevance of BBB in infection/immune system

BBB protects from microorganism invasion to reduce risk of infection but also prevents passage of antibodies --> impede ability to fight CNS infection so BBB becomes leakier in inflammation/infection


What is the relevance of BBB in drug delivery

Many drugs unable to cross BBB due to ABCs which act as extruders
Dopamine broken down enzymatically after import --> Ldopa used for Parkinson's (not enzymatically broken down) --> more passes into brain parenchyma


What is the choroid plexus (structure)

Layer of cuboid epithelial cells surrounding core of capillaries and connective tissue stroma of pia


The choroid plexus epithelial cells are continuous with epdendymal cells lining ventricles, describe this ependymal lining

Formed by single layer of glial cells which may form squamous/cuboid/columnar epithelia depending on site within ventricular system, cells are ciliated on luminal surface and linked by Gap junction and some TJs apically


Describe choroid plexus vessels, compare to BBB vessels

Fenestrated but apical TJs between choroid ependymal epithelial cells restricts intercellular transport
TJs more permeable than those in BBB so blood CSF leakier than BB


Describe transport across Blood CSF barrier

All molecules in blood enter CSF at rate inversely proportional to molecular weight i.e. Plasma proteins enter CSF (i.e. pinocytosis or active transport) but their conc are lower than in blood plasma
Transport mainly vesicular and form choroid plexus side to CSF


Describe the meningeal blood CSF barrier

Between subdural blood and CSF e.g. blood vessels of dura fenestrated but outer cells of arachnoid have TJs --> physical barrier between subarachnoid space and superficial dural layers


How is CSF separated from blood in subarachnoid space

Blood vessels in arachnoid and on pial surface have TKs like in BBB (but no astrocytes or pericytes)


Describe when and how CSF brain barrier exists, what are the implications whne it disappears

Only in fetus: neuroependymal cells linked by strap junctions restricted larger molecuels e.g. protein (cells flatten in development so no barrier between CSF and neural tissue in adulthood --> CSF and interstital fluid in equilibrium (but diffusion decreases with square of distance)


What parts of brain and spinal cord filled with CSF

Ventricles and subarachnoid space


What are the functions of CSF

Shock absorber protects brain from sudden pressure changes
Reduces effective weight of brain
Partially buffers changes in volume of other compartments --> prevent rises in intracranial pressure
Contributes to supply of immune components/nutrients and removal of metabolic waste productions
Medium for diffusion of signalling molecules e.g. NT


Compare CSF composition to plasma

Lower K+
More acidic
Fewer AA and lower protein conc
(relies on effective blood CSF barrier)


How is CSF made, what makes the largest contribution

Secretion of CSF from cells of choroid plexus (most prominent) and ventricular ependyma, and ultrafiltration of blood plasma through choroidal capillaries


Describe passage of CNS from choroid plexus in lateral ventricles to subarachnoid space

From lateral ventricle via interventricular foramen --> 3rd ventricle --> posteriorly through cerebral aqueduct --> 4th ventricle --> median foramen of Magendie and lateral foramina of Luschk --> subarachnoid space


What are cisterns

CSF filled spaces in brain


What are arachnoid villi/granulations

Protrusions of arachnoid mater on dorsal aspect of brain piercing inner meningeal layer of dura to lie within dural venous sinuses --> points of reabsorption of CSF into venous system


How can CCSF diffuse into nasal lymphatics

Along olfactory neural tracts (through cribiform plate) extending into nasal mucosa --> allow CSF to diffuse into nasal lymphatics


What is hydrocephalus (cause and effects)

Increase in CSF volume, due to impaired absorption within ventricular system of beyond
Results in raised intracranial pressure, white matter damage