Program in Neuroscience, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
J Neurol Sci. 2011 Jul 15;306(1-2):129-37. doi: 10.1016/j.jns.2011.03.025. Epub 2011 Apr 8.
Radiation effectively treats brain tumors and other pathologies but dose and treatment plans are limited by normal tissue injury, a major cause of morbidity in survivors. Clinically significant normal tissue injury can occur even with therapies that target pathological tissue and limit out-of-target irradiation. Elucidating the mechanisms underlying normal tissue injury is facilitated by studying the effects of focal irradiation and comparing irradiated and un-irradiated tissue in experimental animals. Young adult rats were irradiated using the Leksell Gamma Knife® with a 10 Gy maximum dose directed at the left hippocampus and shaped to minimize irradiation contralaterally. At least 95% of targeted hippocampus received ≥3 Gy, while all points in the contralateral hippocampus received <0.3 Gy. Neuronal and microglial markers of damage were assessed in the targeted and contralateral hemispheres of Gamma Knife®-treated rats and compared to non-irradiated controls. Acute cell death and sustained changes in neurogenesis and in microglia occurred in the dentate gyrus of the targeted, but not the contralateral, hippocampus, providing experimental evidence that focal irradiation at doses received by peri-target regions during targeted radiation therapy produces robust normal tissue responses. Additional studies using this approach will facilitate assessment of in vivo dose responses and the cellular and molecular mechanisms of radiation-induced brain injury.
辐射有效地治疗脑肿瘤和其他病变，但剂量和治疗计划受到正常组织损伤的限制，这是幸存者发病率的主要原因。即使针对病理性组织并限制靶外照射的治疗方法，也会发生临床意义上的重要正常组织损伤。通过研究聚焦照射的影响并比较实验动物中照射和未照射组织，可以促进对正常组织损伤机制的阐明。使用 Leksell Gamma Knife®对年轻成年大鼠进行照射，最大剂量为 10 Gy，靶向左侧海马体，并进行塑形以尽量减少对侧照射。目标海马体的至少 95%区域接受≥3 Gy 的照射，而对侧海马体的所有点均接受<0.3 Gy 的照射。在接受 Gamma Knife®治疗的大鼠的靶向和对侧半球中评估了神经元和小胶质细胞损伤标志物，并与未照射的对照组进行了比较。在靶向但非对侧海马体的齿状回中发生了急性细胞死亡和神经发生以及小胶质细胞的持续变化，为聚焦照射在靶向放射治疗期间靶区周围区域接受的剂量会产生强烈的正常组织反应提供了实验证据。使用这种方法的进一步研究将有助于评估体内剂量反应以及辐射诱导脑损伤的细胞和分子机制。
