The polyamine inhibitor alpha-difluoromethylornithine modulates hippocampus-dependent function after single and combined injuries

Susanna Rosi, Ryan Ferguson, Kelly Fishman, Antino Allen, Jacob Raber, John R. Fike

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Exposure to uncontrolled irradiation in a radiologic terrorism scenario, a natural disaster or a nuclear battlefield, will likely be concomitantly superimposed on other types of injury, such as trauma. In the central nervous system, radiation combined injury (RCI) involving irradiation and traumatic brain injury may have a multifaceted character. This may entail cellular and molecular changes that are associated with cognitive performance, including changes in neurogenesis and the expression of the plasticity-related immediate early gene Arc. Because traumatic stimuli initiate a characteristic early increase in polyamine metabolism, we hypothesized that treatment with the polyamine inhibitor alpha-difluoromethylornithine (DFMO) would reduce the adverse effects of single or combined injury on hippocampus structure and function. Hippocampal dependent cognitive impairments were quantified with the Morris water maze and showed that DFMO effectively reversed cognitive impairments after all injuries, particularly traumatic brain injury. Similar results were seen with respect to the expression of Arc protein, but not neurogenesis. Given that polyamines have been found to modulate inflammatory responses in the brain we also assessed the numbers of total and newly born activated microglia, and found reduced numbers of newly born cells. While the mechanisms responsible for the improvement in cognition after DFMO treatment are not yet clear, the present study provides new and compelling data regarding the potential use of DFMO as a potential countermeasure against the adverse effects of single or combined injury.

Original languageEnglish (US)
Article numbere31094
JournalPLoS One
Volume7
Issue number1
DOIs
StatePublished - Jan 27 2012

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alpha-difluoromethylornithine
Eflornithine
Polyamines
hippocampus
polyamines
Hippocampus
neurogenesis
brain
cognition
Brain
Wounds and Injuries
irradiation
adverse effects
terrorism
Neurogenesis
neuroglia
disasters
Irradiation
Terrorism
central nervous system

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

The polyamine inhibitor alpha-difluoromethylornithine modulates hippocampus-dependent function after single and combined injuries. / Rosi, Susanna; Ferguson, Ryan; Fishman, Kelly; Allen, Antino; Raber, Jacob; Fike, John R.

In: PLoS One, Vol. 7, No. 1, e31094, 27.01.2012.

Research output: Contribution to journalArticle

Rosi, Susanna ; Ferguson, Ryan ; Fishman, Kelly ; Allen, Antino ; Raber, Jacob ; Fike, John R. / The polyamine inhibitor alpha-difluoromethylornithine modulates hippocampus-dependent function after single and combined injuries. In: PLoS One. 2012 ; Vol. 7, No. 1.
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