Behavioral recovery from traumatic brain injury after membrane reconstruction using polyethylene glycol |
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Authors: | Andrew O Koob Julia M Colby Richard B Borgens |
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Institution: | (1) Center for Paralysis Research, Program in Neuroscience, Purdue University, West Lafayette, IN 47907, USA;(2) Center for Paralysis Research, Department of Basic Medical Sciences, Purdue University, West Lafayette, IN 47907, USA;(3) Center for Paralysis Research, Department of Basic Medical Sciences, Department of Biomedical Engineering, Weldon School of Biomedical Engineering, School of Veterinary Medicine, Purdue University, West Lafayette, IN 47907, USA;(4) Stein Institute for Research on Aging, University of California, San Diego, La Jolla, CA 92093, USA |
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Abstract: | Polyethylene glycol (PEG; 2000 MW, 30% by volume) has been shown to mechanically repair damaged cellular membranes and reduce
secondary axotomy after traumatic brain and spinal cord injury (TBI and SCI respectively). This repair is achieved following
spontaneous reassembly of cell membranes made possible by the action of targeted hydrophilic polymers which first seal the
compromised portion of the plasmalemma, and secondarily, allow the lipidic core of the compromised membranes to resolve into
each other. Here we compared PEG-treated to untreated rats using a computer-managed open-field behavioral test subsequent
to a standardized brain injury. Animals were evaluated after a 2-, 4-, and 6-hour delay in treatment after TBI. Treated animals
receive a single subcutaneous injection of PEG. When treated within 2 hours of the injury, injured PEG-treated rats showed
statistically significant improvement in their exploratory behavior recorded in the activity box when compared to untreated
but brain-injured controls. A delay of 4 hours reduced this level of achievement, but a statistically significant improvement
due to PEG injection was still clearly evident in most outcome measures compared at the various evaluation times. A further
delay of 2 more hours, however, eradicated the beneficial effects of PEG injection as revealed using this behavioral assessment.
Thus, there appears to be a critical window of time in which PEG administration after TBI can provide neuroprotection resulting
in an enhanced functional recovery. As is often seen in clinically applied acute treatments for trauma, the earlier the intervention
can be applied, the better the outcome. |
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