Blood brain barrier Flashcards
What is the point of the blood brain barrier?
to regulate and protect the microenvironment of the brain
BBB can be divided into the ____ barrier and the ____ barrier at the choroid plexus.
BBB can be divided into the vascular/endothelial barrier and the epithelial barrier at the choroid plexus.
What is the choroid plexus?
Specialised secretory epithelium found in each of the four brain ventricles.
It actively generates about 700 mL of cerebral spinal fluid (CSF) per day
Endothelial cells line the capillaries, arterioles and venules and are characterised by the presence of tight junctions. What do these TJ’s do?
result in a high transendothelial electrical resistance and
a decreased paracellular permeability
What ensheathes cerebral microvasculature and protects against hypoxia and aglycaemia?
Astrocytic end feet
What does the restrictive ability of the blood brain barrier unfortunately eliminate?
tissue nourishment usually provided by the plasma
Give some surface transporters that can allow access to the brain across the blood brain barrier?
cation channels ion symports ion antiports facilitated diffusion active transport active transport active antiport transport receptor mediated endocytosis
Give some processes in which substances can pass to the brain via the blood brain barrier without the use of transporters
Residual leakiness Fluid phase endocytosis Adsorptive endocytosis Membrane diffusion Saturable transport
Explain residual leakiness
Involves extracellular pathways - allows an eliquilibrium between plasma and brain fluids for otherwise impermeable proteins such as albumin
What is fluid phase endocytosis?
During receptor-mediated/adsorbative endocytosis, a small amount of extracellular fluid is transported within the endocyte across the epithelium
What is adsorbative endocytosis?
> occurs after chemical, anoxic and physical insults
largely a pathological process in BBB endothelia.
toxic glycoproteins or polycations bind to the blood surface of the endothelium and are endocytosed and routed to intracellular membrane compartments such as lysosomes, endosomes and Golgi for further metabolism etc.
(process whereby viruses gain access to the CNS)
Accumulation of substances in brain interstitial fluids is the net difference between their ____ and ____
influx and efflux
Give some functions of efflux systems in the brain
regulating levels of nutrients and minerals in the CSF;
detoxifying the CNS / reinforcing the impermeability of the BBB against circulating toxins;
contribute substances to the circulation in an endocrine-like manner, such as is illustrated by TNF-a and corticotrophin-releasing hormone (CRH).
Give some transporters involved in brain-blood transport at the BBB
GAT2 for GABA
SERT for Serotonin
NET for norepinephrine
ABC for xenobiotics
What are the major pathways for efflux across the BBB?
> Cerebrospinal fluid readsorption
Membrane diffusion
Lymphatic drainage