Abstract：
:Fractionated partial or whole-brain irradiation (fWBI) is a widely used, effective treatment for primary and metastatic brain tumors, but it also produces radiation-induced brain injury, including cognitive impairment. Radiation-induced neural changes are particularly problematic for elderly brain tumor survivors who also experience age-dependent cognitive impairment. Accordingly, we investigated i] radiation-induced cognitive impairment, and ii] potential biomarkers of radiation-induced brain injury in a rat model of aging. Fischer 344 x Brown Norway rats received fractionated whole-brain irradiation (fWBI rats, 40 Gy, 8 fractions over 4 weeks) or sham-irradiation (Sham-IR rats) at 12 months of age; all analyses were performed at 26-30 months of age. Spatial learning and memory were measured using the Morris water maze (MWM), hippocampal metabolites were measured using proton magnetic resonance spectroscopy ((1)H MRS), and hippocampal glutamate receptor subunits were evaluated using Western blots. Young rats (7-10 months old) were included to control for age effects. The results revealed that both Sham-IR and fWBI rats exhibited age-dependent impairments in MWM performance; fWBI induced additional impairments in the reversal MWM. (1)H MRS revealed age-dependent decreases in neuronal markers, increases in glial markers, but no detectable fWBI-dependent changes. Western blot analysis revealed age-dependent, but not fWBI-dependent, glutamate subunit declines. Although previous studies demonstrated fWBI-induced changes in cognition, glutamate subunits, and brain metabolites in younger rats, age-dependent changes in these parameters appear to mask their detection in old rats, a phenomenon also likely to occur in elderly fWBI patients >70 years of age.
journal_name
Brain Resjournal_title
Brain researchauthors
Shi L,Olson J,D'Agostino R Jr,Linville C,Nicolle MM,Robbins ME,Wheeler KT,Brunso-Bechtold JKdoi
10.1016/j.brainres.2011.02.034subject
Has Abstractpub_date
2011-04-18 00:00:00pages
307-16eissn
0006-8993issn
1872-6240pii
S0006-8993(11)00361-1journal_volume
1385pub_type
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