With
ANY BRAINS AT ALL in the stroke medical world we could use this to deliver much smaller boluses of tPA, lessening the bleed risk considerably. But since we have NO BRAINS IN STROKE, nothing will occur because of this news.
NO leadership, NO strategy, NO advances in stroke. It is what we get because we have
fucking failures of stroke associations.
http://neurosciencenews.com/ultrasound-brain-activity-5994/
Summary: A new
study outlines how researchers have been able to deliver concentrated
amounts of drugs directly into the brains of rats by using ultrasound.
Source: Johns Hopkins Medicine.
Ultrasound pulses activate release of drugs from nanoparticles.
Biomedical engineers at Johns Hopkins report they have worked out a
noninvasive way to release and deliver concentrated amounts of a drug to
the brain of rats in a temporary, localized manner using ultrasound.
The method first “cages” a drug inside tiny, biodegradable
“nanoparticles,” then activates its release through precisely targeted
sound waves, such as those used to painlessly and noninvasively create
images of internal organs.
Because most psychoactive drugs could be delivered this way, as well
as many other types of drugs, the researchers say their method has the
potential to advance many therapies and research studies inside and
outside the brain.
They also say that their method should minimize a drug’s side effects
because the drug’s release is concentrated in a small area of the body,
so the total amount of drug administered can be much lower. And because
the individual components of the technology — including the use of the
specific biomaterials, ultrasound and FDA-approved drugs — have already
been tested in people and found to be safe, the researchers believe
their method could be brought into clinical use more quickly than usual:
They hope to start the regulatory approval process within the next year
or two.
“If further testing of our combination method works in humans, it
will not only give us a way to direct medications to specific areas of
the brain, but will also let us learn a lot more about the function of
each brain area,” says Jordan Green, Ph.D., associate professor of
biomedical engineering, who is also a member of the Kimmel Cancer Center
and the Institute for Nanobiotechnology.
Details of the research are published on Jan. 23 in the journal
Nano Letters.
The new research, Green says, was designed to further advance means
of getting drugs safely to the brain, a delicate and challenging organ
to treat. To protect itself from infectious agents — and from swelling
that can be caused by the immune system, for example — the brain is
surrounded by a molecular fence, called the blood-brain barrier (BBB),
which lines the surface of every blood vessel feeding the brain. Only
very small drug molecules that dissolve in oil can get through the
fence, along with gases. Because of this, most drugs developed for
treating brain disorders fit those criteria but are dispersed to all
parts of the brain — and the rest of the body, where they may be
unneeded and unwanted.
Raag Airan, M.D., Ph.D., assistant professor of radiology at Stanford
University Medical Center and co-author of the paper, says: “When
working with a patient who has post-traumatic stress disorder, for
example, it would be nice to quiet down the overactive part of the brain
— for instance, the amygdala — during talk therapy sessions. Current
technologies can at best quiet down half of the brain at a time, so they
are too nonspecific to be useful in this setting.”
In the new study, the researchers took a cue from previous use of
nanoparticles and ultrasound to deliver chemotherapeutic drugs to tumors
under the skin. In their latest experiments, Green’s group designed
nanoparticles with an outer expandable “cage” made of a biodegradable
plastic, whose molecular building blocks are oil-loving at one end and
water-loving at the other. The oil-loving ends cling together and form
an expandable sphere with the water-loving ends on the outside. The
oil-loving ends bind the drug to be delivered, which in this case was
propofol, an anesthetic commonly used to treat seizures in people.
The center of the cage was filled with the liquid perfluoropentane.
When the sound waves of ultrasound — delivered noninvasively across the
scalp and skull with FDA-approved devices — strike perfluoropentane in
the center of the nanoparticles, the liquid transforms to a gas,
expanding the surrounding cage and letting the propofol escape.
Before testing their idea on animals, Green and his colleagues
fine-tuned their ultrasound protocol by testing nanoparticles in plastic
tubes, seeking to pinpoint pulses of the right power and frequency to
release adequate amounts of the drug without being strong enough to
damage the BBB, a known effect of high-powered ultrasound.
They also tested the distribution of the nanoparticles in rats by
adding a fluorescent dye to the particles and measuring the amount of
dye found in blood and organ samples over time. The majority of the
particles ended up in the spleen and liver, which are important
housekeeping organs in the body. As expected, particles were not found
in the brain because they are too big to pass through the BBB. Instead,
the researchers were relying on propofol’s own ability to pass through
the BBB once released locally from the nanoparticles.
To see whether their method could provide medical relief to live
animals, they then gave rats a drug that causes seizures, followed by
the propofol-laden nanoparticles. They used MRI to guide their
application of the ultrasound to the rat brain and thus release the drug
from nanoparticles floating through infiltrating blood vessels. As soon
as they applied the ultrasound, the seizure activity of the rats calmed
down.
When
drug-laden nanoparticles (left) absorb energy from ultrasound waves,
their liquid center (green) turns to gas and expands the particles
(right), loosening their exterior and releasing the drug (blue).
NeuroscienceNews.com image is credited to Raag Airan.
“These experiments show the effectiveness of this method to
manipulate the function of brain cells through the precise delivery of
drugs,” says Green. “In humans, ultrasound machines can target a volume
as small as a few millimeters cubed, less than one ten-thousandth of the
brain.”
Airan, who was doing his fellowship and residency at The Johns
Hopkins Hospital during the study, says that one of the most promising,
immediate applications of the new technology could be for the “brain
mapping” required before many neurosurgeries. Before a surgeon cuts into
the brain to remove a tumor, for example, he or she needs to know where
not to cut. “Currently, that requires keeping the patient awake, while
the surgeon exposes the brain and probes it with electrodes while
assessing responses. The ultrasound method would allow us to use a drug
like propofol to briefly ‘turn off’ specific areas of the brain one at a
time, prior to the surgery, with nothing more invasive than a needle
stick,” he says.
Because ultrasound, MRI and each component of the nanoparticles have
been approved for other uses in humans, the researchers expect a short
timeline to get their idea to patients, but they acknowledge that its
applications will be somewhat limited by the cost and accessibility of
MRI scans — at least in the short term.
“Our current model requires real-time imaging of the brain while the
ultrasound is being applied,” says Airan. “Based on similar procedures I
already do, that could cost up to $30,000 to $50,000. But we’re working
on software that would allow us to synchronize a single MRI image with
the ultrasound guidance system to decrease the cost significantly.”
Meanwhile, the researchers believe it will still be clinically
relevant in many situations where a drug’s effects are known to last for
weeks. They also expect it to be widely used in brain research to study
and manipulate the function of specific areas of the brain in a
controlled manner.
