Peptide Delivery To The CNS Flashcards
What is the main circulation route of CSF?
Through lateral, third and fourth ventricles
Down around the spinal cord and up through the surface of the brain
What is cerebrospinal fluid?
Blood borne fluid produced in the brain and circulates throughout the brain and spinal cord. It is then absorbed back to the blood circulations
What is pervascular circulation?
Where a portion (5%) of the CSF flows along the perivascular space and extends from the sub-arachnoid space through the brain parenchyma
Where is CSF absorbed back into?
The superior sagittal sinus and other venous structures through arachiod granulation a
What is the function of the CSF?
- supports the brain
- transports nutrients, chemical messengers and waste in and out of the brain
What is the CSF turnover rate?
About 8 hours in humans (1 hour in rats)
How do the components of the CSF differ from plasma?
- protein content in CSF is 100x less than plasma
- plasma contains 50-79g/L of proteins, while CSF only contains 0.5g/L
- CSF contains approximate 0.3% of plasma proteins
- drug metabolism is different from that in plasma
What are the brain barriers?
The structures and functions that
- isolate the CNS from the general circulation
- separate the brain parenchyma from the CSF circulation
- Blood brain barrier
- Blood CSF barrier
- CSF brain barrier
What is the blood brain barrier comprised of?
- endothelial cells packed tightly in brain capillaries that more greatly restrict passage of substances from the bloodstream than endothelial cells in capillaries elsewhere in the body,
- processes from astrocytes surround the epithelial cells of the bbb providing biochemical support to the epithelial cells
What are the structural differences between brain microvescular endothelial cells and normal endothelial cells?
Absence of fenestrations and more extensive tight junctions are found in brain microvascular endothelial cells
What are the functional differences between brain microvescular endothelial cells and normal endothelial cells?
The brain microvescular endothelial cell is
- impermeable to most substances
- sparse pinocytic vesicular transport
- increased expression of transport and carrier proteins: receptor mediated endocytosis
- no gap junctions, only tight junctions
- limited paracellular and Transcellular transport
What is the function of the blood brain barrier?
- Isolates brain from peripheral circulation
- interface between blood that supplies nutrients to the brain and enables the brain to regulate homeostasis of its environment to function properly
- selective permeability to the CNS
- limits central uptake of large molecules
- limits central uptake of hydrophilic compounds
What is the anatomy of the blood CSF barrier?
Tight junction of the choroid plexus cells
What is the function of the blood CSF barrier?
- selective pass of substances from capillaries
- limiting drug penetration through choroid plexus
What is the anatomy of the CSF brain barrier?
- ventricular lining cells
- membrane of brain surface