The AT{sub 1} Receptor Antagonist, L-158,809, Prevents or Ameliorates Fractionated Whole-Brain Irradiation-Induced Cognitive Impairment
- Department of Radiation Oncology, Wake Forest University School of Medicine, Winston-Salem, NC (United States)
- Hypertension and Vascular Research Center, Wake Forest University School of Medicine, Winston-Salem, NC (United States)
- Department of Biostatistical Sciences, Wake Forest University School of Medicine, Winston-Salem, NC (United States)
- Department of Radiology, Wake Forest University School of Medicine, Winston-Salem, NC (United States)
- Center for Biomolecular Imaging, Wake Forest University School of Medicine, Winston-Salem, NC (United States)
Purpose: We hypothesized that administration of the angiotensin type 1 (AT1) receptor antagonist, L-158,809, to young adult male rats would prevent or ameliorate fractionated whole-brain irradiation (WBI)-induced cognitive impairment. Materials and Methods: Groups of 80 young adult male Fischer 344 x Brown Norway (F344xBN) rats, 12-14 weeks old, received either: (1) fractionated WBI; 40 Gy of {gamma} rays in 4 weeks, 2 fractions/week, (2) sham-irradiation; (3) WBI plus L-158,809 (20 mg/L drinking water) starting 3 days prior, during, and for 14, 28, or 54 weeks postirradiation; and (4) sham-irradiation plus L-158,809 for 14, 28, or 54 weeks postirradiation. An additional group of rats (n = 20) received L-158,809 before, during, and for 5 weeks postirradiation, after which they received normal drinking water up to 28 weeks postirradiation. Results: Administration of L-158,809 before, during, and for 28 or 54 weeks after fractionated WBI prevented or ameliorated the radiation-induced cognitive impairment observed 26 and 52 weeks postirradiation. Moreover, giving L-158,809 before, during, and for only 5 weeks postirradiation ameliorated the significant cognitive impairment observed 26 weeks postirradiation. These radiation-induced cognitive impairments occurred without any changes in brain metabolites or gross histologic changes assessed at 28 and 54 weeks postirradiation, respectively. Conclusions: Administering L-158,809 before, during, and after fractionated WBI can prevent or ameliorate the chronic, progressive, cognitive impairment observed in rats at 26 and 52 weeks postirradiation. These findings offer the promise of improving the quality of life for brain tumor patients.
- OSTI ID:
- 21172594
- Journal Information:
- International Journal of Radiation Oncology, Biology and Physics, Vol. 73, Issue 2; Other Information: DOI: 10.1016/j.ijrobp.2008.09.058; PII: S0360-3016(08)03548-7; Copyright (c) 2009 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0360-3016
- Country of Publication:
- United States
- Language:
- English
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