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Alzheimer's, Dementia & Mental Health
Bottleneck Found in Blood Supply Makes Brain
Vulnerable to Strokes, Dementia
Accumulated damage in elderly may lead to memory loss
and a risk of larger stroke
 January 4, 2006 – As people age into their senior
citizen years a puzzling damage to the brain's gray matter is often
detected in brain scans. A team of physicists and neuroscientists at the
University of California, San Diego, think they have found the answer -
a bottleneck in the network of blood vessels in the brain that makes it
vulnerable to strokes. They think it is also part of the dementia
picture in Alzheimer’s and non-Alzheimer’s patients.
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In the study, published this week in the journal
Proceedings of the National Academy of Sciences, the researchers used a
laser technique they developed to precisely monitor changes in blood
flow resulting from an induced blockage in a tiny artery, or arteriole,
in the brains of anesthetized rats. They found that the penetrating
arterioles, which connect the blood vessels on the brain’s surface with
deeper blood vessels, are a vulnerable link in the network.
“The blood vessels on the surface of the brain are
like a collection of city streets that provide multiple paths to get
somewhere,” explained David Kleinfeld, a professor of physics at UCSD,
who led the team. “If one of the vessels is blocked, blood flow quickly
rearranges itself. On the other hand, the penetrating arterioles are
more like freeways. When blocked, the blood flow is stopped or slowed
significantly in a large region round the clot.”
The obstruction of blood flow resulted in damage to
the surrounding brain area, which the researchers report resembled
damage seen in the brains of humans and thought to be the result of
“silent strokes.”
Silent strokes have attracted attention recently
because magnetic resonance imaging has made it possible to follow
changes in the brains of individuals as they age. MRI scans have
revealed that, over time, small holes accumulate in the gray matter of
many patients, including those who have no obvious behavioral signs of a
stroke.
The researchers say their results support the
hypothesis, made by clinicians, that the penetrating arterioles may be
the location of small strokes that cause the death of sections of brain
tissue in humans. The accumulation of damage may lead to memory loss,
and may be a risk factor for having a larger stroke, according to Pat
Lyden, a professor of neurosciences at UCSD’s School of Medicine and
head of the UCSD Stroke Center.
“This damage is an enormous problem,” said Lyden,
who collaborated with Kleinfeld on the study. “We think it is part of
the dementia picture in Alzheimer’s and non-Alzheimer’s patients. But
until now, we had no insight into the mechanism of the damage, and
understanding the mechanism is the first step toward understanding how
to prevent it.”
To determine what happens in the brain during a
stroke, the researchers created a tiny clot in a blood vessel in the
brain of an anesthetized rat. They used focused laser light to excite a
dye they had injected into the bloodstream. A chemical reaction of the
excited dye “nicked” the blood vessel at the target location and
triggered the natural clotting response.
“The technique creates a clot while generating very
little collateral damage,” said Beth Friedman, an associate project
scientist working with Lyden in neurosciences and a contributing author
on the paper. “Then we can study blood flow changes to understand what
is happening in the brain in real time.”
Before and after the formation of the clot, the
researchers tracked the movements of red blood cells using two-photon
fluorescence microscopy. Two-photon fluorescence microscopy is a
powerful imaging tool that uses brief (less than one-trillionth of a
second) laser pulses to peer below the surface of the brain.
In contrast to a previous study, in which the team
showed there was very little disruption in blood flow when a clot formed
in the blood vessels on the surface of the brain, a blockage in the
penetrating arterioles had a significant effect. The flow of red blood
cells was reduced far downstream of the blockage. Because blood flow
cannot simply take alternate routes to compensate for the blockage, the
penetrating arterioles are a bottleneck in the blood supply to gray
matter.
“In this study, we took advantage of being able to
see into individual capillaries in brain tissue,” explained Nozomi
Nishimura, who was a graduate student working with Kleinfeld in physics
at the time of the study. “It is the capillaries, the smallest blood
vessels, that provide the brain cells with oxygen and nutrients. So we
were able to measure the dynamics of blood flow where it really matters
to nerve cells.”
Editor's Notes:
Nishimura was the first author on the study and
is now a postdoctoral fellow at Cornell University working with Chris
Schaffer, an assistant professor of biomedical engineering. Schaffer,
who also contributed to the study, was an assistant project scientist
working with Kleinfeld and Lyden at the time of the discovery.
Source:
University of California, San Diego
The study was supported by the National
Institutes of Health and the National Science Foundation.
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