Injecting nanoparticles in the blood curbed brain swelling in mice

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Injecting a swarm of nanoparticles
into the blood of someone who has suffered a brain injury may one day help to
limit the damage —
if experimental results in mice can be translated to humans. In mice, these nanoparticles
seemed to reduce dangerous swelling by distracting immune cells from rushing to an
injured brain.

The results, described
online January 10 in the Annals of
Neurology
, hint that the inflammation-fighting nanoparticles might someday
make powerful medicine, says John Kessler, a neurologist at Northwestern
Medicine in Chicago. “All the data we have now suggest that they’re going to be
safe, and they’re likely to work” for people, Kessler says. “But we don’t know
that yet.”

After an injury, tissue
often swells as immune cells flock to the damage. Swelling of the brain can be dangerous
because the brain is contained within the skull and “there’s no place to go,” Kessler
says. The resulting pressure can be deadly.

But nanoparticles might serve
as an immune-cell distraction, the results in mice suggest.

Two to three hours after a
head injury, mice received injections of tiny biodegradable particles made of
an FDA-approved polymer —
the same sort that’s used in some dissolving sutures. Instead of rushing toward
the brain, a certain type of immune cell called monocytes began turning their
sights on these invaders. These monocytes engulfed the nanoparticles, and the
cells and their cargo got packed off to the spleen for elimination, the
researchers found. Because these nanoparticles are quickly taken out of
circulation, the researchers injected the mice again one and two days later, in
an effort to ease inflammation that might crop back up in the days after the
injury.

Mice that received the nanoparticles fared better after their brain injuries
than mice that didn’t get the nanoparticles. Ten weeks after the injury, the
damaged spots themselves were about half as big as the spots in mice that
didn’t receive the treatment, suggesting the damage was stalled in the mice
that got nanoparticles.

Other tests showed that both
brain swelling and scarring were less severe in mice that had received
nanoparticles. Mice’s vision cells performed better in response to light. And behavior
improved, too. Mice were able to walk better across a ladder if they had received
the nanoparticle decoys. The scope of the animals’ improvements was “a much
bigger effect than you actually expected or hoped for,” Kessler says.

Other potential nanoparticle therapies rely on tethering drugs or other cargo to the
nanoparticles themselves (SN: 3/7/19).
But in this study, the nanoparticles were bare. That’s “different from what we
typically think of as a nanoparticle treatment,” says Forrest Kievit, a
biomedical engineer at the University of Nebraska–Lincoln. That simplicity might make the manufacturing
of these particles more straightforward than other, more complicated
nanoparticles, a benefit for potential clinical trials.

Kievit cautions, however,
that there are many differences between mice and human brain injuries: the type
and severity of the injuries and the timelines for recovery are different, for
instance. And the ways that the brain suffers after a hard hit involves more
than just a harmful immune response. Toxic substances can accumulate and spread
to unaffected areas, for instance.

Still, Kessler is optimistic
that these nanoparticles hold promise not just for treating brain injuries, but
also for a wide range of ailments that involve a potentially damaging immune
response. In 2014, researchers found that nanoparticles
distracted monocytes from causing inflammation in other circumstances in mice. Similar nanoparticles seemed to
improve mice’s heart health after undergoing a blockage that mimics a heart
attack. Nanoparticles also seemed to ease signs of inflammatory bowel disease,
and boosted survival of mice infected with West Nile virus.

There are few ways to treat traumatic
brain injuries, Kessler says. “There’s nothing that’s really been able to make
a dent in this disease. That’s why it would be so exciting if it really works.”

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