New nanoparticle could save lives, limit brain damage by ‘rebooting’ brain blood flow

Researchers at Rice University are conducting tests on a molecule they believe could play an important role in limiting brain damage in a wide variety of injuries. The nanoparticle, polyethylene glycol-hydrophilic carbon clusters (hereafter referred to as PEG-HCC) is already being tested as a means of enhancing certain cancer treatments. The ability to reduce/prevent brain damage, however, could be even more important.

Explaining what PEG-HCC does requires a brief discussion of reactive oxygen species (ROS) molecules. ROS molecules, including free radicals, are chemically reactive molecules that contain oxygen. The human body produces a certain number of ROS through the normal metabolization of oxygen; cells contain a variety of antioxidant enzymes specifically to neutralize ROS molecules. ROS are important to a number of processes in the human body, including apoptosis (programmed cell death) and wound repair. Platelets release ROS into the bloodstream to “recruit” platelets and leukocytes to an injury.

So long as the body remains in equilibrium and the circulatory system is functioning properly these molecules aren’t a threat. When the circulatory system stops functioning properly, that changes — and it changes quickly. Any trauma that significantly reduces blood flow to the brain, either due to stroke or major damage elsewhere, kicks off what’s known as an ischemic cascade. One of the major effects of such a cascade is the release of huge numbers of ROS molecules. Any damage to the brain’s vascular system exacerbates the problem; inadequate circulation means that local antioxidant “stockpiles” are quickly depleted.

Early stroke treatment focuses on breaking down clots precisely because restoring circulation is the only way to stop the ischemic cascade and flush the free radicals into the wider circulatory system where they can be properly broken down. One of the critical limitations of this approach, however, is that proper blood flow doesn’t automatically or instantly stop a cascade. Reperfusion, the act of restoring blood flow to a damaged area, actually leads to further damage as the body reacts to sudden concentrations of toxic byproducts released by necrosis and cell death.

The graph above shows relative levels of superoxide in an individual who suffers a traumatic brain injury (TBI) with and without low blood pressure (hypotension). Note that superoxide levels spike when blood pressure drops, fall when blood is restored and oxidation begins, but then rise considerably at the so-called “Third Strike” point. That “third strike” is the body’s wider response to the damage done by the initial cascade.

PEG-HCC doesn’t short-circuit this entire process, but it functions by neutralizing the ROS that exacerbate much of the damage. It’s far more efficient than the body’s natural defenses. SOD, the superoxide-neutralizing enzyme we naturally produce, functions on a 1:1 ratio and neutralizes one molecule at a time. One molecule of PEG-HCC is designed to neutralize hundreds of thousands of superoxide molecules.

“This is the most remarkably effective thing I’ve ever seen,” said Thomas Kent, the paper’s co-author. “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.”

PEG-HCC has a half-life of 2-3 hours and to date shows no signs of toxicity. Further tests are ongoing, and the nanoparticle is still years away from deployment. What this demonstrates, however, is that cutting-edge molecular biology can create medical treatments that act with far greater precision than anything we’ve deployed to date. If it works, PEG-HCC could be an extremely important tool for saving lives after an earthquake, mudslide, or building collapse. The ischemic cascade that damages brain tissue in a stroke is responsible for what’s known as crush syndrome, an extremely destructive condition that often kills individuals pinned under building rubble unless the damaged limbs are amputated swiftly.