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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.

    [email protected]

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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


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