Aging attenuates radiation-induced expression of pro-inflammatory mediators in rat brain

The present study was designed to examine the effect of aging on radiation-induced expression of pro-inflammatory mediators in rat brain. Male F344 × BN rats (4, 16, and 24 months of age) received either whole brain irradiation with a single dose of 10 Gy γ-rays or sham-irradiation, and were maintained for 4, 8, and 24 h post-irradiation. The mRNA expression levels of various pro-inflammatory mediators such as cytokines, adhesion molecules, chemokine, and matrix metalloproteinase were analyzed by quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR). The acute inflammatory responses to irradiation, including overexpression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, monocyte chemoattractant protein-1 (MCP-1), and matrix metalloproteinase-9 (MMP-9) were markedly attenuated in the hippocampus of middle-aged and old rats compared with young groups. Specifically, a significant age-dependent decrease in TNF-α expression was detected 8 and 24 h after irradiation and a similar age-related attenuation was observed in IL-1β, ICAM-1, and VCAM-1 expression 4 and 8 h post-irradiation. MCP-1 expression was reduced 4 h post-irradiation and MMP-9 expression at 8 h post-irradiation. These results provide evidence for the first time that radiation-induced pro-inflammatory responses in the brain are suppressed in aged animals.