Brain physiology
To remember:
Cranium: CNS brain Vertebral column: spine
Dura: outer tough, Arachnoid: middle layer
Astrocytes: spec cells
Pericytes: integrity of BBB and control blood flow
BBB controls water, ions and hormone flow into brain, ensures composition of interstitial
fluids
Occludin and claudin: transmembrane proteins for transp into brain
TMD1 and NBD1
ATP binding domain in efflux and conformational changes! Alters protein
Chemo: intrathecal, lipid sol paracellular, nanoparticles, alter BBB
Decision making: NAc and prefrontal cortex
Impulsivity: orbitofrontal frontal and medial prefrontal cortex
Where is the CNS in the brain?
Cranium
Where is the CNS in the spinal cord?
vertebral column
What are the two components of the CNS?
brain and spinal cord
What covers the brain and spinal cord?
3 protective layers of connective tissue
called the meninges
What is the meninges and what is it made up of?
dura matter:
tough outermost layer, thick and durable membrane
protective barrier
Arachnoid mater:
located beneath the dura matter
web-like structure
protects underlying structures
Pia matter:
innermost layer
closely attached to the surface of the brain and spinal cord
thin delicate membrane
sits on the brain
provides nourishment to the nervous tissue through blood vessels
What is an epidural?
pain relief
administered into the epidural space of the lower spine
Drugs used for epidural pain relief?
bupivacaine HCl
Ropivacaine HCl
Are epidurals dangerous?
spinal cord extends 2/3 the length of the spinal column
in the lower 1/3 there are individual neurones
, so epidurals in this area is safe
What is CSF?
taking a sample of cerebral spinal fluid
looks at the fluid surrounding the brain and spinal cord
What section of the spinal cord has individual neurons?
lower 1/3
Where do we insert the epidural and why?
lower 1/3 spinal cord
avoid potential damage to spinal cord
What is the structure of the BBB?
astrocytes: specialized cells, surrounds the blood vessels in the brain, releases chemical
signals that regulate tight junctions
pericytes: found on the outside of blood vessels in the brain, regulates blood flow and
maintains the BBB integrity
basement membrane: provides structural support, overall integrity of BBB
tight junctions: protein complexes that seal gaps between endothelial cells, creates a barrier
to prevent free flow of substances between these cells
endothelial cells: inner lining, tightly packed forming a continuous layer, no fenestrations
only tight junctions are found here
capillaries: blood supply
What are fenestrations?
not found in BBB
gaps in the endothelial cells
let out molecules from capillaries
What is the function of the BBB?
maintain homeostasis CNS
restricting movement of water, ions, hormones etc from the blood to the brain
ensures composition of the brain interstitial fluids which is optimal for neurone
function
o e.g. [Na+] [K+]
limits brain exposure to noxious circulating compounds
o e.g. drugs, dietary and environmental xenobiotics and carcinogens
What type of molecule can travel across the BBB?
only small hydrophilic ions/molecules by passive diffusion
o e.g. propofol for anaesthetic
can pass through the tight junctions (paracellular route)
other molecules must pass transcellular
What is occludin and claudin?
transmembrane proteins
regulates paracellular transport of ions and molecules across the BBB
in tight junctions
How does propofol enter the brain?
general anaesthetic
by passive diffusion across the BBB
What are physicochemical characteristics that aid drug diffusion across the BBB?
Low molecular weight: <400-500Da
Optimal lipophilicity: LogP of 1.5-2.5
To remember:
Cranium: CNS brain Vertebral column: spine
Dura: outer tough, Arachnoid: middle layer
Astrocytes: spec cells
Pericytes: integrity of BBB and control blood flow
BBB controls water, ions and hormone flow into brain, ensures composition of interstitial
fluids
Occludin and claudin: transmembrane proteins for transp into brain
TMD1 and NBD1
ATP binding domain in efflux and conformational changes! Alters protein
Chemo: intrathecal, lipid sol paracellular, nanoparticles, alter BBB
Decision making: NAc and prefrontal cortex
Impulsivity: orbitofrontal frontal and medial prefrontal cortex
Where is the CNS in the brain?
Cranium
Where is the CNS in the spinal cord?
vertebral column
What are the two components of the CNS?
brain and spinal cord
What covers the brain and spinal cord?
3 protective layers of connective tissue
called the meninges
What is the meninges and what is it made up of?
dura matter:
tough outermost layer, thick and durable membrane
protective barrier
Arachnoid mater:
located beneath the dura matter
web-like structure
protects underlying structures
Pia matter:
innermost layer
closely attached to the surface of the brain and spinal cord
thin delicate membrane
sits on the brain
provides nourishment to the nervous tissue through blood vessels
What is an epidural?
pain relief
administered into the epidural space of the lower spine
Drugs used for epidural pain relief?
bupivacaine HCl
Ropivacaine HCl
Are epidurals dangerous?
spinal cord extends 2/3 the length of the spinal column
in the lower 1/3 there are individual neurones
, so epidurals in this area is safe
What is CSF?
taking a sample of cerebral spinal fluid
looks at the fluid surrounding the brain and spinal cord
What section of the spinal cord has individual neurons?
lower 1/3
Where do we insert the epidural and why?
lower 1/3 spinal cord
avoid potential damage to spinal cord
What is the structure of the BBB?
astrocytes: specialized cells, surrounds the blood vessels in the brain, releases chemical
signals that regulate tight junctions
pericytes: found on the outside of blood vessels in the brain, regulates blood flow and
maintains the BBB integrity
basement membrane: provides structural support, overall integrity of BBB
tight junctions: protein complexes that seal gaps between endothelial cells, creates a barrier
to prevent free flow of substances between these cells
endothelial cells: inner lining, tightly packed forming a continuous layer, no fenestrations
only tight junctions are found here
capillaries: blood supply
What are fenestrations?
not found in BBB
gaps in the endothelial cells
let out molecules from capillaries
What is the function of the BBB?
maintain homeostasis CNS
restricting movement of water, ions, hormones etc from the blood to the brain
ensures composition of the brain interstitial fluids which is optimal for neurone
function
o e.g. [Na+] [K+]
limits brain exposure to noxious circulating compounds
o e.g. drugs, dietary and environmental xenobiotics and carcinogens
What type of molecule can travel across the BBB?
only small hydrophilic ions/molecules by passive diffusion
o e.g. propofol for anaesthetic
can pass through the tight junctions (paracellular route)
other molecules must pass transcellular
What is occludin and claudin?
transmembrane proteins
regulates paracellular transport of ions and molecules across the BBB
in tight junctions
How does propofol enter the brain?
general anaesthetic
by passive diffusion across the BBB
What are physicochemical characteristics that aid drug diffusion across the BBB?
Low molecular weight: <400-500Da
Optimal lipophilicity: LogP of 1.5-2.5
