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Administration of the peroxisomal proliferator-activated receptor gamma agonist pioglitazone during fractionated brain irradiation prevents radiation-induced cognitive impairment.

Zhao W, Payne V, Tommasi E, Diz DI, Hsu FC, Robbins ME

Department of Radiation Oncology, Brain Tumor Center of Excellence, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.

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.

Published 25 December 2006 in Int J Radiat Oncol Biol Phys, 67(1): 6-9.
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