A traffic
jam in a major artery through town is enough to give any commuter
a headache. Traffic jams in the brain’s
arteries can have much more dire consequences and are trickier to
study. Now a technique developed at UCSD precisely creates and images
blood clots in the brain in real time and could make it possible
to understand the brain’s traffic jams—the small strokes
implicated in many forms of dementia, including Alzheimer’s
disease.
The researchers used a laser to trigger the formation of individual
blood clots in tiny arteries in the brains of anesthetized rats
and monitored the resulting changes in blood flow. They say
their study
provides a way to understand small strokes common in elderly humans. Published in the journal Public Library of Science Biology, the
study represents a collaboration between the research groups
of David Kleinfeld, ’84,
professor of physics at UCSD, and Patrick Lyden, professor of neurosciences
at UCSD’s School of Medicine. “Our technique makes it possible, for
the first time, to precisely target individual blood vessels to create
a blood clot while causing very little collateral damage,” explains
Kleinfeld. “We can then follow, in real time, the changes in
blood flow in surrounding vessels that occur as a result of the formation
of a clot in one small artery of the brain.”
“We know from MRI scans that small strokes are very common in the
brains of elderly patients,” adds Lyden. “Such small
strokes have been linked with dementia, and may also put patients
at risk for a major stroke. The power of the technique we
describe in the paper is that it allows us to study the response
of the brain to a stroke in a controlled way. By understanding what
happens, we hope to learn how to prevent the major damage associated
with stroke.”
In the study, the team members used precisely focused laser light
to excite a dye injected into the bloodstream. A chemical reaction
involving the excited dye created a tiny “nick” in the
cells lining the blood vessel at the target location and triggered
the formation of a blood clot. To follow the blood flow in the arteries upstream and downstream
of the clot, the researchers used two-photon fluorescence microscopy—a
powerful imaging tool that uses brief (less than one-trillionth of
a second) laser pulses to peer below the surface of the brain.Remarkably,
immediately
following the formation of the clot, blood flow downstream of the
clot reversed itself. This finding helps to explain clinicians’ observation that
certain regions of the brain seem to be protected from stroke. These
regions have networks of vessels with extensive redundant connections
that permit blood to flow through alternate loops and be pushed in
the opposite direction below a clot, preventing these
regions from being starved of oxygen. Unfortunately, not every region
of our brain has this kind of redundancy. Of course, neither does
our freeway system.  — Sherry Seethaler
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