Antioxidant Nanoparticles Neutralize Superoxide and Restore Blood Flow Following Traumatic Brain Injury

A novel class of potent antioxidant nanoparticles restores brain blood flow and normalizes superoxide and nitric oxide levels in the brains of a rat model of traumatic brain injury (TBI).

Cerebrovascular dysfunction, manifested by reduction in cerebral blood flow (CBF), is a key factor that worsens outcome after TBI, most notably under conditions of hypotension. In a traumatic brain injury, damaged cells release an excessive amount of the reactive oxygen species (ROS) superoxide (SO) into the blood. Healthy organisms balance SO with increased production of the neutralizing enzyme superoxide dismutase (SOD), but even mild brain trauma can release superoxides at levels that overwhelm the brain’s capacity for SOD synthesis.

Based on data accumulated in studies designed to enhance cancer treatment via nanoparticle-based drug delivery, investigators at Rice University (Houston, TX, USA) decided to test their potential for treating TBI. These poly(ethylene glycol)-functionalized hydrophilic carbon clusters (PEG-HCCs) represent a new class of nontoxic, antioxidant carbon-based nanoparticles.

PEG-HCCs were administered to a mild TBI/hypotension/resuscitation rat model during resuscitation, which is a clinically relevant time point. Results published in the August 6, 2012, online edition of the journal ACS Nano revealed that the particles rapidly restored CBF. Along with restoration of CBF, there was a concomitant normalization of superoxide and nitric oxide levels.

“Superoxide is the most deleterious of the reactive oxygen species, as it is the progenitor of many of the others,” said senior author Dr. James M. Tour, professor of chemistry, mechanical engineering, and materials science at Rice University. “If you do not deal with SO, it forms peroxynitrite and hydrogen peroxide. SO is the upstream precursor to many of the downstream problems. 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 two to three nanometers wide and 30 to 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 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 Dr. Tour. “They are certainly exacerbated when there is trauma with massive blood loss.”

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