Intravenous Polyethylene Glycol Inhibits the Loss of Cerebral Cells after Brain Injury

Abstract

We have tested the effectiveness of polyethylene glycol (PEG) to restore the integrity of neuronal membranes after mechanical damage secondary to severe traumatic brain injury (TBI) produced by a standardized head injury model in rats. We provide additional detail on the standardization of this model, particularly the use and storage of foam bedding that serves to both support the animal during the impact procedure-and as a dampener to the acceleration of the brass weight. Further, we employed a dye exclusion technique using ethidium bromide (EB; quantitative evaluation) and horseradish peroxidase (HRP; qualitative evaluation). Both have been successfully used previously to evaluate neural injury in the spinal cord since they enter cells when their plasma membranes are damaged. We quantified EB labeling (90 microM in 110 microL of sterile saline) after injection into the left lateral ventricle of the rat brain 2 h after injury. At six h after injection and 8 h after injury, the animals were sacrificed and the brains were analyzed. In the injured rat brain, EB entered cells lining and medial to the ventricles, particularly the axons of the corpus callosum. There was minimal EB labeling in uninjured control brains, limited to cells lining the luminal surfaces of the ventricles. Intravenous injections of PEG (1 cc of saline, 30% by volume, 2000 MW) immediately after severe TBI resulted in significantly decreased EB uptake compared with injured control animals. A similar result was achieved using the larger marker, HRP. PEG-treated brains closely resembled those of uninjured animals.