Intravenous polyethylene glycol successfully treats severe acceleration-induced brain injury in rats as assessed by magnetic resonance imaging.
OBJECTIVE
Polyethylene glycol (PEG) is a nontoxic molecule with known efficacy as a cell membrane sealant, improving histological and behavioral outcomes in trauma models. Diffusion-weighted (DW) magnetic resonance imaging (MRI) is the most sensitive method of detecting in vivo diffuse axonal injury (DAI), where a decreased apparent diffusion coefficient (ADC) of water reflects cytotoxic edema. We use DW-MRI to assess severe DAI in rats treated with a single acute postinjury injection of PEG.


METHODS
Rats were divided into uninjured, injured saline-treated, and injured PEG-treated groups. Injury groups received a severe brain injury using an impact-acceleration weight-drop model. Saline or PEG was administered acutely as a single intravenous dose to injured saline-treated and injured PEG-treated groups, respectively. DW-MRI analysis was performed at postinjury day 7 with a 9.4-T magnet. ADC was calculated for cortex, corpus callosum/hippocampus, and thalamus in each group.


RESULTS
An expected decrease in ADC, representing cytotoxic edema, was observed in the injured saline-treated group. The injured PEG-treated group demonstrated no decrease in ADC relative to the uninjured rats, and the difference between ADC in saline and PEG-treated groups reached significance for all 3 zones of assessed brain. Differences were seen grossly between injured saline-treated and injured PEG-treated groups on representative color-mapped ADC images.


CONCLUSIONS
A single intravenous dose of PEG dramatically limits sequelae of severe acceleration-induced brain injury--in this case, assessed by cytotoxic edema on DW-MRI--by intervening at the primary injury level of neuronal membrane disruption. This outcome is unprecedented, as no prior treatments for DAI have demonstrated similar efficacy. DAI treatment with intravenous PEG may have future clinical relevance and warrants further investigation.
Smucker
Philip
P
Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. phil@smucker1.com
Hekmatyar
S K
SK
Bansal
Navin
N
Rodgers
Richard B
RB
Shapiro
Scott A
SA
Borgens
Richard B
RB
D000054:Acceleration / Q000009:adverse effects*; D000818:Animals; D006259:Craniocerebral Trauma / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D038524:Diffusion Magnetic Resonance Imaging; D004195:Disease Models, Animal; D007275:Injections, Intravenous / Q000379:methods; D008297:Male; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D051381:Rats; D012997:Solvents / Q000008:administration & dosage*
D012997:Solvents; D011092:Polyethylene Glycols