a Departments of Neurobiology and Anatomy.
Radiat Res. 2014 Jul;182(1):60-71. doi: 10.1667/RR13662.1. Epub 2014 Jun 17.
Patients treated with whole-brain irradiation often develop cognitive deficits that are presumed to result from normal tissue injury. Age is a risk factor for these side effects. We compared the cognitive effects of fractionated whole-brain irradiation (300 kV X rays) in rats irradiated either as young adults or in middle age. A deficit in object memory was apparent at 3 months in rats irradiated as young adults, however, no comparable deficit was apparent in rats irradiated in middle age. In addition, the deficit in object memory in young adults was no longer apparent at 6 and 12 months after fractionated whole-brain irradiation and no radiation-induced deficit was detectable in a spatial memory task at any time, regardless of age at time of irradiation. Thus, clinically relevant fractionated whole-brain irradiation in adult rats resulted in early-delayed cognitive changes that were heterogeneous, transient and age-dependent. The results of the current and previous studies of radiation-induced cognitive changes support the continued investigation and validation of rodent models of radiation-induced brain injury, which are critical for developing and testing new therapies for treatment-induced cognitive dysfunction in cancer survivors.
接受全脑照射的患者常出现认知功能障碍，据推测这是正常组织损伤的结果。年龄是这些副作用的一个风险因素。我们比较了年轻成年期或中年期接受分割全脑照射（300 kV X 射线）的大鼠的认知影响。在年轻成年期接受照射的大鼠中，在 3 个月时出现了物体记忆缺陷，但在中年期接受照射的大鼠中则没有出现类似的缺陷。此外，在分割全脑照射后 6 个月和 12 个月，年轻成年大鼠的物体记忆缺陷不再明显，无论在照射时的年龄如何，在任何时间都无法检测到空间记忆任务中的辐射诱导缺陷。因此，在成年大鼠中进行临床相关的分割全脑照射会导致早期延迟的认知变化，这些变化具有异质性、短暂性和年龄依赖性。目前和以前关于放射性认知变化的研究结果支持对放射性脑损伤的啮齿动物模型进行持续的研究和验证，这对于开发和测试癌症幸存者治疗诱导认知功能障碍的新疗法至关重要。
