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.
bradd@nmr.mgh.harvard.edu
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
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 of
the cortex according as it is most active, but of this we
know nothing.”
-- W. James, 1890
Blood flow and the organ of thought
Brain Facts:
18F-2-Deoxyglucose
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
bodyХs energy.
Question:
Can ТactivationsУ account for this
high energy consumption?
Alavi, A. & Reivich, M.
Seminars in Nuclear Medicine
XXXII: 2-5, 2002
Slide courtesy of M. Raichle
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
The route of blood to the head
The route of blood within the head
Circle of
Willis
10 mm
The route of blood within the head
T1
T2
The route of blood within the head
The route of blood within the head
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)
Scale of the circulatory system
Large arteries (e.g., carotid): .5 - 1 cm
Arterioles: 10 - 50 um
Scale of the circulatory system
Capillaries: 5 - 10 um (RBC)
Scale of the circulatory system
Venules/veins
The route of blood within the head
The route of blood within the head
The route of blood within the head
The route of blood within the head
Pial arteriolar anastomoses
1 mm
From Edvinsson, 1993
AP view: Vertebral artery angiogram
Cortical capillary vasculature
5 mm
Cortical neural structure
5 mm
Cortical capillary vasculature
Grey
matter
has 2-4
times the
capillary
density
of white
matter
5 mm
Cerebellar
Vasculature
Inferior
Olivary
Nucleus and
Inferior
Cerebellar
Peduncle
From Duvernoy, 1995
2 mm
Cerebellar
Histology
Blue = myelin
Pink = neuropil
1 mm
From Duvernoy, 1995
500 mm
From Duvernoy, 1995
100 mm
Cerebellar Cortical Histology
Cerebellar histology and
vascularization
Molecular
Layer
Purkinje Cells
50 mm
From Duvernoy, 1995
Granular
Layer
Capillary density in rat brain is
proportional to metabolic rate
High levels of CBF
Cochlear nucleus, mammillary body, cortex
Low levels of CBF
Hypothalamus, cerebellum, medulla
High levels of CMRglu
Cochlear nucleus, mammillary body,
cortex
Low levels of CMRglu
Hypothalamus, cerebellum, medulla
From Edvinsson, 1993
Flow of CSF
CSF return to venous blood
Large vessels in subarachnoid space
Blood Brain Barrier
• What cerebral capillaries have:
– Tight continuous quintuple-layered intercellular
junctions
– low wall thickness (0.2 um)
– higher mitochondrial content
– thick basement membrane
• What cerebral capillaries don’t have:
– fenestrations
– lots of vesicles
– fluid-filled bulk transport channels
Blood Brain Barrier
• Allows passage/transport of small
molecules (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
Measurement of blood flow to
the brain
• Aorta 90cm/s, ICA 40cm/s, arterioles 10250mm/s, capillaries 1mm/s
• Transcranial doppler ultrasound
Cerebral autoregulation
• CBF remains constant over wide range of
change in arterial pressure
Flow is regulated by arteriolar smooth
muscle
Arterioles: 10 - 50 um
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 must
move upstream to supplying arteriole
Changes in cerebral blood flow
can be prompted by
• Change in hemical mileu/blood gases
– Arterial hypercarbia/tissue acidosis/hypoxemia
• Neurotransmitter systems
– Autonomic nervous system
• Sympathetic (NE, Neuropeptide Y)
• Parasympathetic (ACh, VIP)
– Dopamine vs noradrenaline
– Serotonin
• Localized neural activity
Global perfusion increase
from hypothalamus
and brain stem
Sympathetic innervation of blood vessels
from hypothalamus
and brain stem
NE (fast, short acting)
&
NPY (slow, longer lasting)
From Wilson-Pauwels, 1997
Sympathetic innervation of cortical pial vessels
from hypothalamus
and brain stem
Noradrenergic
Dopaminergic
Neurotransmitter systems