2013B04 Discuss the physiological significance of the blood brain barrier.



·         Intro: BBB

·         Components

·         Circumventricular organs

·         Freely permeable

·         Selectively permeable

·         Impermeable


Intro: blood-brain barrier


·   Barrier between blood and brain ECF for homeostasis and protection

·   Multiple components

·   Variable permeability

·   Entry by diffusion or active transport


·   Neonate: immaturity

·   Elderly: degeneration

·   Profound hypertension: damage

·   Meningeal disease: inflammation (MS), infection (meningitis) -> damage

Factors conferring permeability

·   ↑C1 (e.g. ↑dose)

·   ↓C2 (e.g. glucose utilisation)

·   ↑Area (not under control)

·   ↓Thickness (e.g. dysfunction)

·   ↑Lipid solubility (e.g. propofol)

·   ↓Molecular weight (e.g. O2)

·   Unionised (e.g. propofol 98%)

·   Non-polar (e.g. CO2)

·   Not protein bound (e.g. ketamine)


Components of blood-brain-barrier

Physical barrier

·   Endothelial cells: tight junctions, no fenestrae, low rate of transcytosis

·   Basement membrane: negative charge

·   Astrocyte foot processes

(cf. blood-CSF barrier: tight junctions between choroid epithelioctes)

Immune cells

·   Astrocytes = antigen-presenting cell: activates T and B cells

·   Microglia = macrophage: phagocytosis, inflammation, chemotaxis


·   GLUT-1: constitutively expressed, ensures priority supply of glucose

·   Ion channels: control [Na+], [K+], [Ca2+] – preserve polarity, prevent excitotoxicity


·   e.g. MAO, AChE

·   Prevent circulating neurotransmitters from entering brain


Circumventricular organs:


·   “Outside” the blood-brain barrier, near the fourth ventricle

·   i.e. permeable vessels allow contact with blood


·   Posterior pituitary: secretes ADH, oxytocin

·   Area postrema (contains CTZ): circulating toxin induces vomiting

·   OVLT, SFO: ↑osmolality -> ↑activation of hypothalamus -> ↑ADH release

·   Pineal gland: secretes melatonin

·   Medial eminence


Free permeability:


·   Travels up osmotic gradient

Very low MW

·   e.g. O2

·   e.g. CO2 (e.g. CO2 -> H+ for control of breathing)

Very lipid soluble

·   e.g. ketones, propofol


Selective permeability = homeostasis:


·   Ions are charged hence impermeable

·   Active influx (e.g. Mg2+, Cl-) and efflux

·   For control of ECF environment (e.g. metabolic acidosis in exercise -> ↑H+)

·   For preservation of cell polarity

·   For preservation of brain cell volume, proportional to brain ECF [Na+]


·   Glucose: via GLUT1, limited capacity

o Too much -> glycosylation

o Too little -> unconsciousness

·   Amino acids: for neurotransmitter synthesis

·   Lipids: for membrane maintenance


Impermeability = protection:


·   Brain NTs barred from circulation (e.g. brain noradrenaline metabolized by MAO)

·   Peripheral NTs barred from brain (e.g. ingested serotonin metabolized by MAO)


·   Endogenous neurotoxins (e.g. bilirubin)

·   Exogenous neurotoxins (e.g. cholera toxin)


·   Physical barrier

·   Immune cells

Many drugs

·   e.g. muscle relaxants (large, polar)


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