Title: How does blood flow inform us about brain function?
1How 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_at_nmr.mgh.harvard
.edu
2How 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
3Blood 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
4Blood flow and the organ of thought
Slide courtesy of M. Raichle
5Blood 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
6The route of blood to the head
7The route of blood within the head
8Circle of Willis
9The route of blood within the head
10T1 T2
11The route of blood within the head
12The route of blood within the head
13Scale 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)
14Scale of the circulatory system
Large arteries (e.g., carotid) .5 - 1
cm Arterioles 10 - 50 um
15Scale of the circulatory system
Capillaries 5 - 10 um (RBC)
16Scale of the circulatory system
Venules/veins
17The route of blood within the head
18The route of blood within the head
19The route of blood within the head
20The route of blood within the head
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28Pial arteriolar anastomoses
1 mm
From Edvinsson, 1993
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30AP view Vertebral artery angiogram
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32Cortical capillary vasculature
5 mm
33Cortical neural structure
5 mm
34Cortical capillary vasculature
Grey matter has 2-4 times the capillary density
of white matter
5 mm
35Cerebellar Vasculature
36Inferior Olivary Nucleus and Inferior Cerebellar
Peduncle
2 mm
From Duvernoy, 1995
37Cerebellar Histology
Blue myelin
Pink neuropil
1 mm
From Duvernoy, 1995
38100 mm
500 mm
From Duvernoy, 1995
39Cerebellar Cortical Histology
40Cerebellar histology and vascularization
Molecular Layer
Purkinje Cells
Granular Layer
From Duvernoy, 1995
41Capillary density in rat brain is proportional to
metabolic rate
High levels of CMRglu Cochlear nucleus,
mammillary body, cortex
High levels of CBF Cochlear nucleus, mammillary
body, cortex
Low levels of CMRglu Hypothalamus, cerebellum,
medulla
Low levels of CBF Hypothalamus, cerebellum,
medulla
From Edvinsson, 1993
42Flow of CSF
43CSF return to venous blood
44Large vessels in subarachnoid space
45Blood 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 dont have
- fenestrations
- lots of vesicles
- fluid-filled bulk transport channels
46Blood 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
47Measurement of blood flow to the brain
- Aorta 90cm/s, ICA 40cm/s, arterioles 10-250mm/s,
capillaries 1mm/s - Transcranial doppler ultrasound
48Cerebral autoregulation
- CBF remains constant over wide range of change in
arterial pressure
49Flow is regulated by arteriolar smooth muscle
Arterioles 10 - 50 um
50Sites 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
51Changes 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
52Global perfusion increase
from hypothalamus and brain stem
53Sympathetic innervation of blood vessels
from hypothalamus and brain stem
NE (fast, short acting) NPY (slow, longer
lasting)
From Wilson-Pauwels, 1997
54Sympathetic innervation of cortical pial vessels
from hypothalamus and brain stem
Noradrenergic Dopaminergic
55Neurotransmitter systems