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Printable Handouts
Navigable Slide Index
- Introduction
- Astrocytes and cerebral blood vessels
- Regulation of the blood supply of the brain
- CBF needs to be matched with metabolism
- Functions of astrocytes
- Astrocytes control separate domains, have endfeet
- Astrocytes respond to glutamate from synapses
- Astrocyte endfeet enwrap all CBV
- Rudolf Virchow's paper - 1858
- Astrocytes relationship with blood vessels
- Astrocyte endfeet: specialized contacts with CBV
- Arteriole vessel wall
- The modulators of CBF
- Brain slices
- Poiseullee's law: impact of vessel diameter on flow
- The methods of photolysis of caged Ca2+
- Two-photon uncaging of DM-Nitrophen
- Astrocyte calcium waves cause vasoconstriction
- Astrocyte endfeet induced vascular constrictions
- Norepinephrine effect on arteriole constriction
- Effect of Ca2+ chelation
- Astrocytes and vascular dynamics
- Impact of astrocyte induced constrictions
- Confirmation: Ca2+ waves cause vasoconstriction
- Astrocyte can induce dilations and constrictions
- Dilation is more complicated
- Oxygen dynamics in vivo
- O2 effect on astrocyte control of the vasculature
- CBF is tightly coupled to the NADH-NAD ratio
- Effect of O2 and lactate on vasculature control
- Tissue pO2 effect on synaptic activity (1)
- Tissue pO2 effect on synaptic activity (2)
- Complex regulation of dilation by metabolism
- pO2 and vessel responses to Ca2+ signals
- mGluR activation in high O2
- mGluR activation in low O2
- Low pO2 converts constrictions to dilation
- Astrocytes express enzymes that make PGE2
- Astrocytes express both COX1 and COX 2
- Low pO2 dilations require PGE2 synthesis (1)
- Low pO2 dilations require PGE2 synthesis (2)
- Where are the PGT expressed?
- Astrocytes and neurons express PGT
- Lower pO2 increase NADH, lactate and PGE2
- Is there a relationship between lactate and PGE2?
- Lactate, PGE2 and NADH increased in lower pO2
- Glycolysis coincides with vasodilation in low O2
- Lactate is necessary for PGE2 dilation
- Vasoconstrictions aren't observed in low O2
- Blocking A1 receptors raises Pr only in low O2
- Adenosine effect on vascular constriction
- PGE2 clearance by PGT is hindered by lactate
- Lactate in high O2 enables vaso-conversion
- Blocking PGT - high O2
- Blocking PGT - high O2 + adenosine + t34
- Blocking PGT - after washing
- Summary data
- Conclusion
- Ca2+ pathways (1)
- Ca2+ pathways (2)
- Brain metabolic state dictates astrocyte control
- Acknowledgements
Topics Covered
- The regulation of the blood supply of the brain
- Functions of astrocytes
- Astrocytes all have endfeet
- Astrocyte endfeet enwrap all cerebral blood vessels
- The modulators of cerebral blood flow
- Astrocyte calcium waves cause vasoconstriction
- Astrocytes and vascular dynamics
- Functional impact of astrocyte induced constrictions
- Dilation is more complicated
- Can changing levels of O2 and lactate modify vasculature control by astrocytes?
- Tissue pO2 levels
- Complex regulation of dilation by metabolism
- Changing oxygen levels
- Astrocytes express both cyclooxygenase -1 and -2
- Prostaglandin transporters
- Is there a relationship between lactate and PGE2?
- Why are vasoconstrictions not observed in low O2?
- Brain metabolic state dictates the polarity of astrocyte control over the cerebrovasculature
Talk Citation
MacVicar, B. (2010, August 11). Astrocyte control of cerebral blood vessels [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved November 21, 2024, from https://doi.org/10.69645/KVUI3308.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Brian MacVicar has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
A selection of talks on Neuroscience
Transcript
Please wait while the transcript is being prepared...
0:00
My name is Brian MacVicar
and I'm going to
talk to you about
the "Control of Cerebral
Blood Vessels by Astrocytes".
0:10
This image shows a view of
astrocytes taken with
a two-photon laser
scanning microscope.
The astrocytes are shown in
green and the blood
vessels in red.
Astrocytes are small
star-shaped cells that
are distributed
throughout the brain
and actually outnumbered
nerve cells.
0:30
It is only in the last
few years that we
have shown that astrocytes
actually, directly
interact with cerebral
blood vessels and can
modulate cerebral blood flow.
The question of how
cerebral blood flow is
regulated is a very old
question in neuroscience.
Over 100 years ago,
Roy and Sherrington,
shown in this picture
in the slide,
published a paper
in which they said,
"the brain possesses
an intrinsic mechanism
which its vascular supply
can be varied locally
in correspondence
with local variations of
functional activity".
This observation was seminal in
describing how
cerebral blood flow
can be modified in response
to the local activity
in nerve cells.
This, of course,
is now the basis
for functional
neuroanatomical techniques
which MRI or PET techniques are
used to map out areas
of brain activity.
1:28
It is very important
that cerebral
blood flow is matched to the
metabolism of the brain tissue,
even though the brain is only
2 percent of bodyweight,
15 percent of the blood
flow goes to the brain.
The oxygen consumption and
glucose consumption are
also extremely high,
20 percent and 50 percent of
the body demands, respectively.
If there is a mismatch of
cerebral blood flow to
the metabolic demand,
it has terrible consequences on
the functioning of the brain.
It was thought that
vascular dementia results
from a decrease in
blood flow that
does not match the
metabolic demands and leads
to synaptic disruption and
cognitive dysfunction.
In ischemic stroke and after
subarachnoid hemorrhage,
there are unexplained decreases
in cerebral blood
flow that causes
secondary effects and lead
to terrible consequences
to patients.