Inquiring minds want to know if this is also releasing the pericytes clamping down on the capilliaries.
http://www.medicalnewstoday.com/releases/249439.php
A nanoparticle developed at Rice University and tested in collaboration
with Baylor College of Medicine (BCM) may bring great benefits to the
emergency treatment of brain-injury victims, even those with mild
injuries.
Combined polyethylene glycol-hydrophilic carbon clusters (PEG-HCC), already being tested to enhance cancer
treatment, are also adept antioxidants. In animal studies, injections
of PEG-HCC during initial treatment after an injury helped restore
balance to the brain's vascular system.
The results were reported this month in the American Chemical Society journal ACS Nano.
A PEG-HCC infusion that quickly stabilizes blood flow in the brain would
be a significant advance for emergency care workers and battlefield
medics, said Rice chemist and co-author James Tour.
"This might be a first line of defense against reactive oxygen species
(ROS) that are always overstimulated during a medical trauma, whether
that be to an accident victim or an injured soldier," said Tour, Rice's
T.T. and W.F. Chao Chair in Chemistry as well as a professor of
mechanical engineering and materials science and of computer science.
"They're certainly exacerbated when there's trauma with massive blood
loss."
In a traumatic brain injury,
cells release an excessive amount of an ROS known as superoxide (SO)
into the blood. Superoxides are toxic free radicals, molecules with one
unpaired electron, that the immune system normally uses to kill invading
microorganisms. Healthy organisms balance SO with superoxide dismutase
(SOD), an enzyme that neutralizes it. But even mild brain trauma can
release superoxides at levels that overwhelm the brain's natural
defenses.
"Superoxide is the most deleterious of the reactive oxygen species, as
it's the progenitor of many of the others," Tour said. "If you don't
deal with SO, it forms peroxynitrite and hydrogen peroxide. SO is the
upstream precursor to many of the downstream problems."
SO affects the autoregulatory mechanism that manages the sensitive
circulation system in the brain. Normally, vessels dilate when blood
pressure is low and constrict when high to maintain an equilibrium, but a
lack of regulation can lead to brain damage beyond what may have been
caused by the initial trauma.
"There are many facets of brain injury that ultimately determine how
much damage there will be," said Thomas Kent, the paper's co-author, a
BCM professor of neurology and chief of neurology at the Michael E.
DeBakey Veterans Affairs Medical Center in Houston. "One is the initial
injury, and that's pretty much done in minutes. But a number of things
that happen later often make things worse, and that's when we can
intervene."
Kent cited as an example the second burst of free radicals that can
occur after post-injury resuscitation. "That's what we can treat: the
further injury that happens because of the necessity of restoring
somebody's blood pressure, which provides oxygen that leads to more
damaging free radicals."
In tests, the researchers found PEG-HCC nanoparticles immediately and
completely quenched superoxide activity and allowed the autoregulatory
system to quickly regain its balance. Tour said ROS molecules readily
combine with PEG-HCCs, generating "an innocuous carbon double bond, so
it's really radical annihilation. There's no such mechanism in biology."
While an SOD enzyme can alter only one superoxide molecule at a time, a
single PEG-HCC about the size of a large protein at 2-3 nanometers wide
and 30-40 nanometers long can quench hundreds or thousands. "This is an
occasion where a nano-sized package is doing something that no small
drug or protein could do, underscoring the efficacy of active nano-based
drugs."
"This is the most remarkably effective thing I've ever seen," Kent said.
"Literally within minutes of injecting it, the cerebral blood flow is
back to normal, and we can keep it there with just a simple second
injection. In the end, we've normalized the free radicals while
preserving nitric oxide (which is essential to autoregulation). These
particles showed the antioxidant mechanism we had previously identified
as predictive of effectiveness."
The first clues to PEG-HCC's antioxidant powers came during nanoparticle
toxicity studies with the MD Anderson Cancer Center. "We noticed they
lowered alkaline phosphatase in the liver," Tour said. "One of our
Baylor colleagues saw this and said, 'Hey, this looks like it's actually
causing the liver cells to live longer than normal.'
"Oxidative destruction of liver cells is normal, so that got us to
thinking these might be really good radical scavengers," Tour said.
Kent said the nanoparticles as tested showed no signs of toxicity, but
any remaining concerns should be answered by further tests. The
researchers found the half-life of PEG-HCCs in the blood - the amount of
time it takes for half the particles to leave the body - to be between
two and three hours. Tests with different cell types in vitro showed no
toxicity, he said.
The research has implications for stroke victims and organ transplant patients as well, Tour said.
Next, the team hopes to have another lab replicate its positive results.
"We've repeated it now three times, and we got the same results, so
we're sure this works in our hands," Kent said.
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