Transcriptomics of Rat Striata 16 h after Gamma Knife Surgery: Distinct Bilateral Effects in the Un-irradiated Striatum

Gamma knife surgery (GKS) is used for treatment of various brain disorders. The effects of gamma irradiation to targeted and un-targeted regions were evaluated by monitoring gene expression changes in the unilateral irradiated (60 Gy) and contralateral un-irradiated striata in the rat. Striata of irradiated and control brains were dissected 16 h post-irradiation for analysis by rat whole genome 44K DNA oligo microarray. Results revealed 230 induced and 144 repressed genes in the irradiated striatum and 432 induced and 239 repressed genes in the un-irradiated striatum. The number of altered genes in un-irradiated striatum was more than that in irradiated striatum. Results of RT-PCR and western analyses suggested that gamma-irradiation caused cellular damage, including oxidative stress, in both striata of both hemispheres. Our present results indicate that unilateral irradiation during GKS produce bilateral effects as early as 16 h, the time-period analyzed, and these molecular changes in the un-irradiated striatum are ample proof.伽玛刀手术（Gamma knife surgery, GKS）可用于治疗多种脑部疾病。本研究通过监测大鼠单侧照射（60 Gy）及对侧未照射纹状体的基因表达变化，评估了伽马辐照对靶向与非靶向区域的影响。于辐照后16小时，解剖取材照射组与对照组大鼠的纹状体，采用大鼠全基因组44K DNA寡核苷酸微阵列进行分析。结果显示，照射侧纹状体中共有230个上调基因与144个下调基因，未照射侧纹状体中则有432个上调基因与239个下调基因。未照射侧纹状体的差异基因数量多于照射侧纹状体。逆转录聚合酶链反应（RT-PCR）与蛋白质印迹分析结果表明，伽马辐照可导致双侧纹状体发生细胞损伤，包括氧化应激。本研究结果表明，伽玛刀手术中的单侧辐照可在分析的早期时间点（16小时）即产生双侧效应，未照射侧纹状体中的这些分子变化即为充分证据。