Source
Department of Radiation Oncology, Brain Tumor Center of Excellence, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
Abstract
PURPOSE:
We hypothesized that administration of the anti-inflammatory peroxisomal proliferator-activated receptor gamma (PPARgamma) agonist pioglitazone (Pio) to adult male rats would inhibit radiation-induced cognitive impairment.
METHODS AND MATERIALS:
Young adult male F344 rats received one of the following: (1) fractionated whole brain irradiation (WBI); 40 or 45 Gy gamma-rays in 4 or 4.5 weeks, respectively, two fractions per week and normal diet; (2) sham-irradiation and normal diet; (3) WBI plus Pio (120 ppm) before, during, and for 4 or 54 weeks postirradiation; (4) sham-irradiation plus Pio; or (5) WBI plus Pio starting 24h after completion of WBI.
RESULTS:
Administration of Pio before, during, and for 4 or 54 weeks after WBI prevented the radiation-induced cognitive impairment. Administration of Pio for 54 weeks starting after completion of fractionated WBI substantially but not significantly reduced the radiation-induced cognitive impairment.
CONCLUSIONS:
These findings offer the promise of improving the quality of life and increasing the therapeutic window for brain tumor patients.