Administration of the peroxisomal proliferator-activated receptor gamma agonist pioglitazone during fractionated brain irradiation prevents radiation-induced cognitive impairment.
OBJECTIVE
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
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.
Zhao
Weiling
W
Department of Radiation Oncology, Brain Tumor Center of Excellence, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
Payne
Valerie
V
Tommasi
Ellen
E
Diz
Debra I
DI
Hsu
Fang-Chi
FC
Robbins
Mike E
ME
D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight; D001921:Brain / Q000187:drug effects / Q000528:radiation effects; D003071:Cognition / Q000187:drug effects / Q000528:radiation effects; D003072:Cognition Disorders / Q000209:etiology / Q000517:prevention & control*; D016371:Cranial Irradiation / Q000009:adverse effects*; D004334:Drug Administration Schedule; D007328:Insulin / Q000097:blood; D008297:Male; D047495:PPAR gamma / Q000819:agonists*; D000077205:Pioglitazone; D011829:Radiation Dosage; D011897:Random Allocation; D051381:Rats; D011916:Rats, Inbred F344; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000627:therapeutic use*
D007328:Insulin; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077205:Pioglitazone