Intravenous polyethylene glycol as a method of treatment for traumatic brain injury
Abstract
Polyethylene glycol (PEG; 30% by volume, 2000 MW) can restore the integrity of neuronal membranes after mechanical damage to the spinal cord. Using a standardized head injury model in rats we provide detail of PEG's neuroprotective qualities in the brain. We describe PEG's ability to reconstitute membrane damage, eliminate axotomy and restore behavioral function after traumatic brain injury (TBI). To test initial cell membrane damage after TBI we employed a dye exclusion technique using ethidium bromide (EB; 90μM in 110μ1 sterile saline). EB was injected into the left lateral ventricle of the rat brain after injury and quantified. In the injured rat brain, EB entered the parenchyma medial to the ventricles, particularly the axons of the corpus callosum. Minimal EB labeling was seen in uninjured control brains, limited to cells lining the luminal surfaces of the ventricles. Injured PEG-treated brains closely resembled those of uninjured animals. To further describe the effect of PEG treatment after injury we performed immunohistochemistry to locate β-Amyloid Precursor Protein (APP). Disrupted anterograde axonal transport and resulting APP accumulation in the retraction bulb is a byproduct of Traumatic Axonal Injury (TAI) in the brain. APP aggregation indicates axonal degeneration as a result of axotomy---a detriment secondary to initial membrane damage that will lead to cell death. PEG treatment after injury can eliminate APP accumulation in specific brain areas of rats receiving TAI. Lastly, to test behavior after injury, we introduced a novel open field chamber to study exploratory behavior of the rat. A fundamental instinct for the laboratory animal is to explore when placed in a new environment and lack of exploratory behavior is an indicator of TBI. The effect of PEG on behavior after injury concatenates with the EB and APP studies. Injured PEG-treated rats showed markedly improved exploratory behavior when compared with injured untreated rats. Injured rats receiving PEG treatment explored more area, spent more time moving, traveled further and broke more beams than injured untreated animals.
Degree
Ph.D.
Advisors
Borgens, Purdue University.
Subject Area
Neurology
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