Maintenance of Blood-brain Barrier Flashcards
How much oxygen is supplied to the brain per minute?
55 ml/100g of tissue/min
Why is there a vast surplus of glucose delivery to the brain?
Because the brain can only metabolise glucose
Ketone bodies can be metabolized if there is a shortage of glucose but glucose is the main nutrient
Blood glucose below what value will lead to loss of consciousness, coma and death?
2 mM
On what levels do you get regulation of cerebral blood flow?
Mechanisms affecting total cerebral blood flow
Mechanisms that relate activity to requirement in specific brain regions by altered localised blood flow
Between what range in mean arterial blood pressure can autoregulation maintain a constant cerebral blood flow?
60-160 mm Hg
Name one important factor to do with the smooth muscle lining arterioles that allows regulation of blood flow.
Myogenic Mechanism – when the smooth muscle surrounding arterioles is stretched, it will contract to maintain a constant blood flow
This occurs when there is a change in blood pressure in the body
What are the two types of control of cerebral blood flow regulation?
Neural and Chemical
What are the four types of neural control of cerebral blood flow?
Vasoconstriction
Sympathetic innervation of the main cerebral arteries – causes vasoconstriction when arterial blood pressure is high
Central cortical neurons – neurons within the brain itself can release neurotransmitters such as catecholamines that cause vasoconstriction
Dopaminergic neurons – produce vasoconstriction (important in regulating differential blood flow to areas of the brain that are more active)
Vasodilation
Facial nerve stimulation – can cause a little bit of vasodilation
What feature do capillaries in the brain have that allow them to contract?
They are surrounded by pericytes, a type of brain macrophage that have several functions e.g. contractile, immune function, transport properties
What do the dopaminergic neurons affecting cerebral blood flow innervate?
Pericytes around capillaries and smooth muscle around arterioles
Dopaminergic neurons cause contraction of pericytes via which receptors?
Aminergic and serotoninergic neurons
Which fibres innervate the main arteries in the brain?
Sympathetic fibres
Name some chemical factors that increase blood flow to particular tissues.
Carbon dioxide NO pH (Low pH causes vasodilation) Anoxia Adenosine K+ Other (e.g. kinins, prostaglandins, histamine, endothelins)
Describe how carbon dioxide indirectly causes vasodilation in the cerebral vessels.
H+ can’t cross the blood-brain barrier but CO2 can
CO2 moves through the blood-brain barrier into the smooth muscle cells.
Within the smooth muscle cells, in the presence of carbonic anhydrase, the CO2 reacts with H2O to form HCO3- and H+
This generated H+ within the smooth muscle cells cause smooth muscle relaxation
Describe how nitric oxide (NO) causes vasodilation.
Nitric oxide stimulates guanylyl cyclase
Guanylyl cyclase converts GTP - cGMP
cGMP causes vasodilation
Where is CSF produced?
Choroid plexus – these are specific cells associated with the ventricles (in particular the lateral ventricles)
What name is given to parts of the brain that receive blood flow like anywhere else but do not have a blood-brain barrier?
Circumventricular organs
Describe the passage of CSF through the ventricular system.
CSF is produced by specialized ependymal cells of the choroid plexus
From lateral it goes through the foramen of Monro to the 3rd ventricle
From the 3rd, CSF flows down the cerebral aqueduct to the 4th ventricle
From the 4th ventricle it enters the subarachnoid space (via medial and lateral apertures) and eventually drains back into the venous system via arachnoid granulation
What is the volume of CSF in a normal person?
80-150 mL
What is the volume of CSF formed per day?
450 mL/day
State three functions of the CSF.
Protection (chemical and physical)
Nutrient provision to neurons
Transport of molecules
Describe the structure of the blood-brain barrier. Which cells are involved?
Capillaries in brain have endothelial cells with very tight junctions, gives tight control of what can pass through capillary wall.
Capillaries also surrounded by pericytes with end-feet running along the capillary wall
When the pericytes contract more likely molecules will leave capillary
What type of molecule can cross the blood-brain barrier easily?
Lipophilic (non-polar)
How do water and glucose cross the blood-brain barrier?
Water pass through aquaporin molecules
Glucose passes through Glut 1 transporters