Intravenous polyethylene glycol successfully treats severe acceleration-induced brain injury in rats as assessed by magnetic resonance imaging

Philip Smucker, S. K. Hekmatyar, Navin Bansal, Richard Rodgers, Scott Shapiro, Richard B. Borgens

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

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. CONCLUSION: 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.

Original languageEnglish
Pages (from-to)984-990
Number of pages7
JournalNeurosurgery
Volume64
Issue number5
DOIs
StatePublished - May 2009

Fingerprint

Brain Injuries
Magnetic Resonance Imaging
Diffuse Axonal Injury
Diffusion Magnetic Resonance Imaging
Edema
Wounds and Injuries
Magnets
Corpus Callosum
Thalamus
Hippocampus
Color
Cell Membrane
Weights and Measures
Injections
Membranes
Water
Brain
Therapeutics

Keywords

  • Apparent diffusion coefficient
  • Cytotoxic edema
  • Diffuse axonal injury
  • Diffusion- weighted imaging
  • Membrane repair
  • Polyethylene glycol
  • Traumatic brain injury

ASJC Scopus subject areas

  • Clinical Neurology
  • Surgery

Cite this

Intravenous polyethylene glycol successfully treats severe acceleration-induced brain injury in rats as assessed by magnetic resonance imaging. / Smucker, Philip; Hekmatyar, S. K.; Bansal, Navin; Rodgers, Richard; Shapiro, Scott; Borgens, Richard B.

In: Neurosurgery, Vol. 64, No. 5, 05.2009, p. 984-990.

Research output: Contribution to journalArticle

Smucker, Philip ; Hekmatyar, S. K. ; Bansal, Navin ; Rodgers, Richard ; Shapiro, Scott ; Borgens, Richard B. / Intravenous polyethylene glycol successfully treats severe acceleration-induced brain injury in rats as assessed by magnetic resonance imaging. In: Neurosurgery. 2009 ; Vol. 64, No. 5. pp. 984-990.
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AU - Smucker, Philip

AU - Hekmatyar, S. K.

AU - Bansal, Navin

AU - Rodgers, Richard

AU - Shapiro, Scott

AU - Borgens, Richard B.

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AB - 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. CONCLUSION: 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.

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KW - Cytotoxic edema

KW - Diffuse axonal injury

KW - Diffusion- weighted imaging

KW - Membrane repair

KW - Polyethylene glycol

KW - Traumatic brain injury

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