Development of a small-animal focal brain irradiation model to study radiation injury and radiation-injury modifiers

Int J Radiat Biol. 2013 Aug;89(8):645-55. doi: 10.3109/09553002.2013.784424. Epub 2013 Apr 16.

Abstract

Purpose: Our aim was to establish an effective small-animal focal brain radiation model for research on brain injuries.

Material and methods: Groups of up to six rats were exposed to a range of doses from 120-40 Gy, at 10 intervals of a 6 MeV electron beam. Open-field motor functions and water maze learning-memory tests were performed after the irradiation at two-week intervals. Morphological changes were detected through repeated magnetic resonance imaging (MRI) monthly and were compared with the histopathological findings to determine if they predicted late microscopic changes.

Results: The development of necrosis proved to be dose-dependent. 120 Gy resulted in serious deterioration within 4 weeks in all rats. Localized necrosis in one hemisphere was detected 2 months after the irradiation with ≥ 70 Gy, and 3 months after 40-60 Gy consistent for all animals. The Morris water maze (MWM) tests proved to be the most sensitive tool for the early detection of a brain functional impairment. MRI screening provided useful information on the development of radiation necrosis, which defined the time point for histological examinations.

Conclusions: The described method permits accurate dose delivery to a definite part in one hemisphere of the brain for six rats at a time. Following complex examinations, a dose of 40 Gy and a follow-up time of 4 months are proposed for investigations on neuroradiation modifiers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / drug effects
  • Brain / pathology
  • Brain / physiopathology
  • Brain / radiation effects*
  • Dose-Response Relationship, Radiation
  • Magnetic Resonance Imaging
  • Male
  • Radiation Injuries, Experimental* / pathology
  • Radiation Injuries, Experimental* / physiopathology
  • Radiation-Protective Agents / pharmacology
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Radiation-Protective Agents