Functional and Structural Improvement with a Catalytic Carbon Nano-Antioxidant in Experimental Traumatic Brain Injury Complicated by Hypotension and Resuscitation
Kimberly Mendoza
University of Texas Medical Branch
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.