A Experimental Study On The Expression Of The Cytokines In The Hippocampus After Whole-brain Irradiation

Objective: To discuss the changes of the cytokines in the acute phage of brain radiation injuries, the expression of rumor necrosis factor- a (TNF- a ) interleukin-1β (IL-1β ) and interleukin-6(IL-6) mRNA in the different doses and times points was observed in the rat hippocampus after whole-brain irradiation.Methods: A model of brain radiation-induced injuries was established in the rat after whole- brain irradiation with the single dose of 4MeV electron beam. The expression of the cytokines in the hippocampus was analyzed semi quantitatively at different times(1, 6, 12,24, 48hours and 7days) and doses( 2Gy, 15Gy and 30Gy) points with reverse-transcription polymerase chain reaction (RT-PCR).Results: The expression of TNF- a,IL-1β and IL-6 mRNA in the hippocampus after whole-brain irradiation was at lower level in normal group and sham irradiation group, and there was no significance between them.The expression of TNF- a reached the peak level in 1 hour, which was 4-11 times as high as the normal group, and began to decrease in 6 hours and then returned to basic level in 12 hours. Its induction by irradiation was in a dose-dependent manner with the dose increase, in contrast to 2Gy and 15Gy groups, almost 2-fold and 1-fold increases in 30Gy group were observed respectively.The expression of IL-1β began to up-regulate in 1 hour and reached the peak level in 6 hours, which was 2-4 times as high as the normal group. Then the level in 12 hours were decreased but higher than that of the normal group, and returned to the normal in 24 hours. A dose-dependent manner was also seen in the course of induction.The expression of IL-6 began to increase only in 6 hours and reached the peak level in 12 hours, which was 2-5 times as high as normal group, returned to the normal. Unlike the expression of TNF- a and IL-1β , its induction level by irradiation continued not to be up-regulated with the dose increase. That of 15Gy group was the highest, one time higher than that of 2Gy and 30Gy groups. Within a week the expression of the three cytokines were not increased significantly again.Conclusion: The expression of TNF- a , IL-1 β and IL-6 mRNA in the rat hippocampus after whole-brain irradiation with the differently single doses was up-regulated significantly and reached sequentially the peak level, whose the times were 1hour, 6hours and 12hours respectively.They returned to the normal level in 24 hours. Among the cytokines, the up-regulated level of TNF- a was the highest. Induction of TNF- a and IL-1β by radiation were in a dose-dependent manner while that of IL-6 was decreased in 30Gy. Our studies suggest that the three pro-inflammatory cytokines may play important role in the mechanisms of acute phage of brain radiation-induced injuries.