International Journal of Radiation Oncology * Biology * Physics
Volume 67, Issue 1 , Pages 6-9, 1 January 2007

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

  • Weiling Zhao, Ph.D.

      Affiliations

    • Department of Radiation Oncology, Brain Tumor Center of Excellence, Wake Forest University School of Medicine, Winston-Salem, NC
    • ,
  • Valerie Payne, B.S.

      Affiliations

    • Department of Radiation Oncology, Brain Tumor Center of Excellence, Wake Forest University School of Medicine, Winston-Salem, NC
    • ,
  • Ellen Tommasi, B.S.

      Affiliations

    • Hypertension and Vascular Disease Center, Wake Forest University School of Medicine, Winston-Salem, NC
    • ,
  • Debra I. Diz, Ph.D.

      Affiliations

    • Hypertension and Vascular Disease Center, Wake Forest University School of Medicine, Winston-Salem, NC
    • ,
  • Fang-Chi Hsu, Ph.D.

      Affiliations

    • Department of Biostatistical Sciences, Wake Forest University School of Medicine, Winston-Salem, NC
    • ,
  • Mike E. Robbins, Ph.D.

      Affiliations

    • Department of Radiation Oncology, Brain Tumor Center of Excellence, Wake Forest University School of Medicine, Winston-Salem, NC
    • Corresponding Author InformationReprint requests to: Mike E. Robbins, M.D., Room 412C NRC, Department of Radiation Oncology, Wake Forest University School of Medicine, Medical Center Blvd, Winston-Salem, NC 27157. Tel: (336) 713-7635; Fax: (336) 713-7639

Received 15 September 2006; received in revised form 21 September 2006; accepted 22 September 2006.

Purpose: We hypothesized that administration of the anti-inflammatory peroxisomal proliferator-activated receptor γ (PPARγ) 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 γ-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.

Keywords: Rat brain, Whole brain irradiation, Cognitive impairment, PPARγ, Pioglitazone

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 Supported by National Institutes of Health grants CA112593 (MER) and HL51952 (DIZ).Conflict of interest: none.

PII: S0360-3016(06)03128-2

doi:10.1016/j.ijrobp.2006.09.036

International Journal of Radiation Oncology * Biology * Physics
Volume 67, Issue 1 , Pages 6-9, 1 January 2007

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