Improved Outcome with a Catalytic Carbon Nano-Antioxidant in Experimental Traumatic Brain Injury Complicated by Hypotension.

Hypotension worsens outcome after all severities of traumatic brain injury (TBI), with loss of cerebral autoregulation a potential contributor. Previously, we demonstrated that intravenous injection of a high capacity catalytic antioxidant, poly(ethylene)glycol conjugated hydrophilic carbon clusters (PEG-HCCs) rapidly restored cerebral perfusion and acutely restored brain oxidative balance in a TBI model complicated by hemorrhagic hypotension without evidence of toxicity. Here, we tested whether these acute effects translated into behavioral and structural benefit. Traumatic Brain Injury was generated by a cortical contusion impactor in 38 Long Evans rats, followed by blood withdrawal to a target mean arterial pressure of 40 mmHG. PEG-HCC (2 mg/kg) or diluent was injected intravenously 80 minutes later at the onset of blood resuscitation followed by another injection 2 hr. later (doses determined in prior studies). Beam walking (performed days 1-5) and Morris Water Maze performance (MWM; performed days 11 - 15) were tested, and lesion size determined at the termination. PEG-HCC treatment nearly completely prevented motor dysfunction (p<.001 vs diluent), improved MWM performance (p<.001; treatment vs time interaction) and reduced lesion size by 61% (p=.054). Here we show that PEG-HCCs treated at a clinically realistic time point (onset of resuscitation) prevented a major portion of the neurological dysfunction induced in this TBI model and appears worthy of additional development as a potential therapeutic agent.