How does blood flow inform us about brain function? - PowerPoint PPT Presentation

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How does blood flow inform us about brain function?

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Title: How does blood flow inform us about brain function?


1
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_at_nmr.mgh.harvard
.edu
2
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
3
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
4
Blood flow and the organ of thought
Slide courtesy of M. Raichle
5
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

6
The route of blood to the head
7
The route of blood within the head
8
Circle of Willis
9
The route of blood within the head
10
T1 T2
11
The route of blood within the head
12
The route of blood within the head
13
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)
14
Scale of the circulatory system
Large arteries (e.g., carotid) .5 - 1
cm Arterioles 10 - 50 um
15
Scale of the circulatory system
Capillaries 5 - 10 um (RBC)
16
Scale of the circulatory system
Venules/veins
17
The route of blood within the head
18
The route of blood within the head
19
The route of blood within the head
20
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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Cortical capillary vasculature
5 mm
33
Cortical neural structure
5 mm
34
Cortical capillary vasculature
Grey matter has 2-4 times the capillary density
of white matter
5 mm
35
Cerebellar Vasculature
36
Inferior Olivary Nucleus and Inferior Cerebellar
Peduncle
2 mm
From Duvernoy, 1995
37
Cerebellar Histology
Blue myelin
Pink neuropil
1 mm
From Duvernoy, 1995
38
100 mm
500 mm
From Duvernoy, 1995
39
Cerebellar Cortical Histology
40
Cerebellar histology and vascularization
Molecular Layer
Purkinje Cells
Granular Layer
From Duvernoy, 1995
41
Capillary 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
42
Flow of CSF
43
CSF return to venous blood
44
Large vessels in subarachnoid space
45
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 dont have
  • fenestrations
  • lots of vesicles
  • fluid-filled bulk transport channels

46
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

47
Measurement of blood flow to the brain
  • Aorta 90cm/s, ICA 40cm/s, arterioles 10-250mm/s,
    capillaries 1mm/s
  • Transcranial doppler ultrasound

48
Cerebral autoregulation
  • CBF remains constant over wide range of change in
    arterial pressure

49
Flow is regulated by arteriolar smooth muscle
Arterioles 10 - 50 um
50
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

51
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

52
Global perfusion increase
from hypothalamus and brain stem
53
Sympathetic innervation of blood vessels
from hypothalamus and brain stem
NE (fast, short acting) NPY (slow, longer
lasting)
From Wilson-Pauwels, 1997
54
Sympathetic innervation of cortical pial vessels
from hypothalamus and brain stem
Noradrenergic Dopaminergic
55
Neurotransmitter systems
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