Download Neuroscience 2b – Cerebral Blood Flow

Neuroscience 2b – Cerebral Blood Flow
Anil Chopra
1. Briefly explain why cerebral blood flow has to be maintained.
2. List the neural and humoral factors, which can participate in cerebral blood flow
regulation.
3. Explain how cerebral blood flow is regulated in response to changes in blood
pressure.
4. Describe by means of a diagram how cerebral blood flow is regulated by the blood
pCO2.
5. Briefly describe the blood-brain barrier and explain its significance.
Oxygen Supply to the brain
-
large percentage of cardiac output (15%) - 55ml/100g tissue/min
if blood flow is reduced by more than 50%, function is impaired.
Total interruption causes unconsciousness in 4 seconds, and irreversible damage in a
few minutes.
The brain is dependant of glucose as only energy source (and ketones also
metabolised but to a small extent). Hypoglycaemia is therefore a large problem (if
lower then 2mM, then unconsciousness, coma and death can result).
Cerebral Blood Flow Regulation
Cerebral blood flow needs to be maintained. It is autoregulated between mean arterial
blood pressures of 60mmHg – 160mmHg
Local autoregulation
This is process by which increases blood flow to parts of the brain that are more
active. It is achieved in a variety of ways
Neural Factors
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sympathetic nervous system (produces vasoconstriction) – only really operates
when blood pressure is high.
parasympathetic branch of cranial nerve VII (produces vasodilation)
Vasoconstriction form neurotransmitters such as dopamine which are released
by the neurones in the brain itself.
Dopaminergic Neurones
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Innervate penetrating arterioles and pericytes around capillaries
Pericytes are form of brain macrophages with diverse activities (e.g. immune
function, transport properties, contractile)
may participate in the diversion of cerebral blood to areas of high activity
Dopamine may cause contraction of pericytes via aminergic and
serotoninergic receptors.
Chemical Factors (likely to be localized)
a) CO2 (indirect)
vasodilator
b) pH (i.e. H+,; lactic acid, etc.)
c) nitric oxide
vasodilator
vasodilator
d) K+
vasodilator
e) adenosine
vasodilator
f) anoxia
vasodilator
g) other (e.g. kinins, prostaglandins, histamine, endothelins)
Blood-Brain Barrier
The blood brain barrier protects the
brain from harmful substances in the
blood (toxins, circulating transmitters)
and maintains ion concentrations.
This is achieved by:
- tight junctions between
endothelial cells (of the
microvasculature)
- astrocyte end-feet
It allows some lipophilic molecules (e.g. alcohol) access to the brain CSF and ECF
but certain hydrophilic substances to enter the CSF and brain ECF by means of
specific transport mechanisms, examples being:
a) water, via aquaporin (AQP1, AQP4) channels
b) glucose, via GLUT1 proteins
c) amino acids, via 3 different transporters
d) electrolytes, via specific transporter systems
Some areas of the brain (collectively called the circumventricular organs, CVO) have
“fenestrated” capillaries and therefore lie outside the blood-brain barrier. E.g. median
eminence region of hypothalamus.
CSF Formation
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Cerebrospinal fluid is formed in the choroid plexus.
The ependymal cells surround the capillaries secrete CSF into the ventricles.
The total volume is between 80-150ml
Serves as
o Protection: a shock absorber
o Nutrition: for neurones
o Transport: of molecules
including waste
products of metabolism.