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首页> 美国卫生研究院文献>Neuro-Oncology >RB-01A PRECLINICAL MODEL OF TRANSIENT EARLY-DELAYED RADIATION EFFECTS FOLLOWING WHOLE BRAIN IRRADIATION IN THE ADULT RAT
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RB-01A PRECLINICAL MODEL OF TRANSIENT EARLY-DELAYED RADIATION EFFECTS FOLLOWING WHOLE BRAIN IRRADIATION IN THE ADULT RAT

机译：RB-01A在成年大鼠全脑辐照后的瞬态早期延迟放射效应的临床模型

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BACKGROUND: Whole brain radiotherapy is a common for metastatic brain cancer. While it prolongs survival, it causes transient early-delayed cognitive deficits termed “beamo” brain. We describe a dose-escalation study that demonstrates a potential preclinical animal model of this clinical phenomenon. METHODS: 3-month old Fisher rats were given a single fraction of 0, 10, 20, or 30G Gray (Gy) whole brain irradiation. The open-field exploration task and the elevated plus maze were performed at 4 months post-irradiation. Declarative memory was tested by novel object recognition at 4- and 7-months post-irradiation. Magnetic resonance imaging, including diffusion tensor imaging (DTI) and spectroscopy (MRS), was obtained at baseline, 4-, and 7-months post-irradiation in controls, 20Gy and 30Gy groups. RESULTS: At 4 months post-irradiation, no differences were found between the groups in either the open-field exploration or the elevated plus maze. There was no difference in novel object recognition between 10Gy and sham controls at 4 months post-irradiation. However, both 20Gy (p = 0.02) and 30Gy (p < 0.02) animals demonstrated memory deficits at this early time-point compared to controls. At 7 months post-irradiation, the 20Gy group performed similar to controls and 10Gy; however, the 30Gy animals (p = 0.01) persisted in their memory impairment. MRS demonstrated increased choline in the corpus callosum in 20Gy (p = 0.08) and in 30Gy (p = 0.01) at 4 months, but normalized by 7 months in all groups. Fractional anisotropy was significantly decreased in the hippocampus of 20Gy (p = 0.02) and 30Gy (p = 0.0002) animals by 7 months, but not before. CONCLUSION: 3-month old rats given 20Gy single whole brain radiation demonstrated transient cognitive impairment similar to that observed in adult patients receiving whole brain irradiation for metastatic disease and may correlate with increased levels of choline in the hippocampus. This may be a promising model in which to test potential therapies for “beamo” brain.
机译：背景：全脑放疗是转移性脑癌的常见病。虽然它可以延长生存期，但会引起短暂的早期认知缺陷，称为“ beamo”大脑。我们描述了一项剂量递增研究，该研究证明了这种临床现象的潜在临床前动物模型。方法：对3个月大的Fisher大鼠进行单次0、10、20或30G Gray（Gy）全脑照射。野外探索任务和高架迷宫在照射后4个月进行。声明性记忆是在照射后4个月和7个月通过新颖的物体识别测试的。在对照组，20Gy和30Gy组中，在基线，照射后4个月和7个月时获得了磁共振成像，包括扩散张量成像（DTI）和光谱学（MRS）。结果：照射后4个月，在野外勘探或高架迷宫中两组之间没有发现差异。照射后4个月，在10Gy和假对照之间在新颖物体识别方面没有差异。但是，与对照组相比，20Gy（p = 0.02）和30Gy（p <0.02）的动物在此早期时间点均表现出记忆力减退。照射后7个月，20Gy组的表现与对照组和10Gy相似；然而，30Gy动物（p = 0.01）持续存在记忆力障碍。 MRS在4个月时显示call骨胆碱在20Gy（p = 0.08）和30Gy（p = 0.01）中增加，但在所有组中均以7个月恢复正常。到7个月之前，但20Gy（p = 0.02）和30Gy（p = 0.0002）动物的海马分数各向异性显着降低，但此之前没有。结论：3个月大的大鼠接受20Gy单次全脑辐射后，表现出短暂的认知障碍，与接受转移性疾病全脑辐射的成年患者所观察到的相似，可能与海马胆碱水平升高有关。这可能是一个有前途的模型，可以在其中测试“ beamo”大脑的潜在疗法。

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