Mitigating effect of EUK-207 on radiation-induced cognitive impairments

Jacob Raber, M. J. Davis, T. Pfankuch, R. Rosenthal, S. R. Doctrow, J. E. Moulder

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

The brain could be exposed to irradiation as part of a nuclear accident, radiological terrorism (dirty bomb scenario) or a medical radiological procedure. In the context of accidents or terrorism, there is considerable interest in compounds that can mitigate radiation-induced injury when treatment is initiated a day or more after the radiation exposure. As it will be challenging to determine the radiation exposure an individual has received within a relatively short time frame, it is also critical that the mitigating agent does not negatively affect individuals, including emergency workers, who might be treated, but who were not exposed. Alterations in hippocampus-dependent cognition often characterize radiation-induced cognitive injury. The catalytic ROS scavenger EUK-207 is a member of the class of metal-containing salen manganese (Mn) complexes that suppress oxidative stress, including in the mitochondria, and have been shown to mitigate radiation dermatitis, promote wound healing in irradiated skin, and mitigate vascular injuries in irradiated lungs. As the effects of EUK-207 against radiation injury in the brain are not known, we assessed the effects of EUK-207 on sham-irradiated animals and the ability of EUK-207 to mitigate radiation-induced cognitive injury. The day following irradiation or sham-irradiation, the mice started to receive EUK-207 and were cognitively tested 3 months following exposure. Mice irradiated at a dose of 15. Gy showed cognitive impairments in the water maze probe trial. EUK-207 mitigated these impairments while not affecting cognitive performance of sham-irradiated mice in the water maze probe trial. Thus, EUK-207 has attractive properties and should be considered an ideal candidate to mitigate radiation-induced cognitive injury.

Original languageEnglish (US)
JournalBehavioural Brain Research
DOIs
StateAccepted/In press - Sep 14 2016

Fingerprint

Radiation
Terrorism
Radiation Injuries
Wounds and Injuries
Radiodermatitis
Radioactive Hazard Release
Nuclear Weapons
Aptitude
Water
Vascular System Injuries
Brain
Cognitive Dysfunction
EUK 207
Wound Healing
Cognition
Accidents
Hippocampus
Mitochondria
Oxidative Stress
Emergencies

ASJC Scopus subject areas

  • Behavioral Neuroscience

Cite this

Raber, J., Davis, M. J., Pfankuch, T., Rosenthal, R., Doctrow, S. R., & Moulder, J. E. (Accepted/In press). Mitigating effect of EUK-207 on radiation-induced cognitive impairments. Behavioural Brain Research. https://doi.org/10.1016/j.bbr.2016.10.038

Mitigating effect of EUK-207 on radiation-induced cognitive impairments. / Raber, Jacob; Davis, M. J.; Pfankuch, T.; Rosenthal, R.; Doctrow, S. R.; Moulder, J. E.

In: Behavioural Brain Research, 14.09.2016.

Research output: Contribution to journalArticle

Raber, Jacob ; Davis, M. J. ; Pfankuch, T. ; Rosenthal, R. ; Doctrow, S. R. ; Moulder, J. E. / Mitigating effect of EUK-207 on radiation-induced cognitive impairments. In: Behavioural Brain Research. 2016.
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