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How does blood flow inform us about
brain function?
Cerebrovascular anatomy & neural regulation of
CNS blood flow
Neurovascular coupling
HST 583
Brad Dickerson, M.D.
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How does blood flow inform us about
brain function?
Cerebrovascular anatomy & neural regulation of CNS
blood flow
Cerebral blood flow: intro
Cerebrovascular anatomy
Neurotransmitter systems & neural regulation
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Blood flow and the organ of thought
blood supply to any part of the cerebral tissue is
varied in accordance with the activity of the chemiccal
changes which underlie the functional action of that
part -- Roy & Sherrington, 1890
We must suppose a very delicate adjustment whereby
the circulation follows the needs of the cerebral
activity. Blood very likely may rush to each region ofthe cortex according as it is most active, but of this we
know nothing. -- W. James, 1890
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Blood flow and the organ of thought
Alavi, A. & Reivich, M.Seminars in Nuclear Medicine
XXXII: 2-5, 2002
18F-2-DeoxyglucoseBrain Facts:
1. The brain is 2% of the body
weight.
2. The brain receives 11% of the
cardiac output.
3. The brain consumes 20% of the
bodys energy.
Question:
Can activationsaccount for this
high energy consumption?
Slide courtesy of M. Raichle
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Blood flow and the organ of thought
The brain requires blood for:
General support of maintenance functions, like
every organ - requires energy (ATP)
Specific localized support of functional activity
related to neural activity - requires energy (ATP)
Blood supplies substrates for energy production:
Glucose and oxygen
~750 ml/min
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The route of blood to the head
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The route of blood within the head
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10 mm
Circle of
Willis
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The route of blood within the head
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T1 T2
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The route of blood within the head
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The route of blood within the head
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Scale of the circulatory system
Aorta: 2.5 cm (~1 in)
Large arteries (e.g., carotid): .5 - 1 cm
Arterioles: 10 - 50 um
Capillaries: 5 - 10 um (RBC)
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Scale of the circulatory system
Large arteries (e.g., carotid): .5 - 1 cm
Arterioles: 10 - 50 um
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Scale of the circulatory system
Capillaries: 5 - 10 um (RBC)
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Scale of the circulatory system
Venules/veins
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The route of blood within the head
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The route of blood within the head
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The route of blood within the head
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The route of blood within the head
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Pial arteriolar anastomoses
1 mm
From Edvinsson, 1993
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AP view: Vertebral artery angiogram
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5 mm
Cortical capillary vasculature
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5 mm
Cortical neural structure
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5 mm
Cortical capillary vasculature
Grey
matter
has 2-4
times the
capillary
density
of whitematter
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CerebellarVasculature
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Inferior
Olivary
Nucleus and
Inferior
Cerebellar
Peduncle
2 mmFrom Duvernoy, 1995
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Cerebellar
Histology
Blue = myelin
Pink = neuropil
1 mmFrom Duvernoy, 1995
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100 mm500 mm From Duvernoy, 1995
C b ll C ti l Hi t l
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Cerebellar Cortical Histology
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Molecular
Layer
Purkinje Cells
Granular
Layer
50 mm
Cerebellar histology and
vascularization
From Duvernoy, 1995
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Capillary density in rat brain is
proportional to metabolic rate
Low levels of CBFHypothalamus, cerebellum, medulla
High levels of CBFCochlear nucleus, mammillary body, cortex
Low levels of CMRgluHypothalamus, cerebellum, medulla
High levels of CMRgluCochlear nucleus, mammillary body,cortex
From Edvinsson, 1993
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Flow of CSF
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CSF return to venous blood
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Large vessels in subarachnoid space
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Blood Brain Barrier What cerebral capillaries have:
Tight continuous quintuple-layered intercellularjunctions
low wall thickness (0.2 um)
higher mitochondrial content
thick basement membrane
What cerebralcapillaries dont have:
fenestrations
lots of vesicles
fluid-filled bulk transport channels
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Blood Brain Barrier
Allows passage/transport of smallmolecules (H2O, O2, CO2), lipophilic
molecules (EtOH, heroin), passive transport
of glucose, active transport of amino
acids/NT precursors
Prevents passage of larger molecules
(dopamine), charged molecules, etc
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Measurement of blood flow to
the brain
Aorta 90cm/s, ICA 40cm/s, arterioles 10-250mm/s, capillaries 1mm/s
Transcranial doppler ultrasound
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Cerebral autoregulation
CBF remains constant over wide range of
change in arterial pressure
l i l d b i l h
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Flow is regulated by arteriolar smooth
muscle
Arterioles: 10 - 50 um
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Sites of CBF Regulation
Large diameter vessels (ANS)
Smaller diameter arterioles, venules
(neurogenic)Must have smooth muscle with appropriate
innervation and receptor site to act upon
If signaling is at capillary level, message mustmove upstream to supplying arteriole
Changes in cerebral blood flo
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Changes in cerebral blood flow
can be prompted by
Change in hemical mileu/blood gases
Arterial hypercarbia/tissue acidosis/hypoxemia
Neurotransmitter systemsAutonomic nervous system
Sympathetic (NE, Neuropeptide Y)
Parasympathetic (ACh, VIP)Dopamine vs noradrenaline
Serotonin
Localized neural activity
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from hypothalamusand brain stem
Global perfusion increase
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NE (fast, short acting)&
NPY(slow, longer lasting)
From Wilson-Pauwels, 1997
from hypothalamusand brain stem
Sympathetic innervation of blood vessels
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Noradrenergic Dopaminergic
from hypothalamusand brain stem
Sympathetic innervation of cortical pial vessels
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Neurotransmitter systems