Application of radiosurgical techniques to produce a primate model of brain lesions.
Application of radiosurgical techniques to produce a primate model of brain lesions.
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DOI：
10.3389/fnsys.2015.00067
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发表时间：
2015
影响因子：
3
通讯作者：
Tanaka M
中科院分区：
文献类型：
--
作者：
Kunimatsu J;Miyamoto N;Ishikawa M;Shirato H;Tanaka M
对离散脑损伤受试者的行为分析提供了有关各种脑功能机制的重要信息。然而，通常难以通过实验在脑深部结构中产生离散病变。在这里，我们表明，放射外科技术，这是作为一种替代治疗脑肿瘤和血管畸形，适用于创建非侵入性病变的实验动物在系统神经科学的研究。我们使用临床直线加速器（LINAC）将高度聚焦的辐射（ISO中心为130-150戈伊）输送到猕猴的额眼野（FEF）。通过在照射前和照射后8个月内沿着磁共振（MR）图像分析眼科表现来评估照射的影响。在平行的组织水肿所示的MR图像，缺陷扫视和顺利追求眼球运动，观察在几天后照射。虽然最初的眼部缺陷迹象在一个月内消失，但在随后的6个月内，组织损伤和眼球运动受损逐渐发展。尸检组织学检查显示，白色物质的大面积坏死和坏死，在较小程度上，在邻近的灰质，这是集中在照射的目标。这些结果表明，LINAC系统是有用的，在实验动物的脑损伤，而合适的辐射参数，以产生更集中的病变需要进一步探索。我们建议使用放射外科技术建立脑病变的动物模型，并讨论了这种技术在人类功能性神经外科治疗的可能用途。
Behavioral analysis of subjects with discrete brain lesions provides important information about the mechanisms of various brain functions. However, it is generally difficult to experimentally produce discrete lesions in deep brain structures. Here we show that a radiosurgical technique, which is used as an alternative treatment for brain tumors and vascular malformations, is applicable to create non-invasive lesions in experimental animals for the research in systems neuroscience. We delivered highly focused radiation (130–150 Gy at ISO center) to the frontal eye field (FEF) of macaque monkeys using a clinical linear accelerator (LINAC). The effects of irradiation were assessed by analyzing oculomotor performance along with magnetic resonance (MR) images before and up to 8 months following irradiation. In parallel with tissue edema indicated by MR images, deficits in saccadic and smooth pursuit eye movements were observed during several days following irradiation. Although initial signs of oculomotor deficits disappeared within a month, damage to the tissue and impaired eye movements gradually developed during the course of the subsequent 6 months. Postmortem histological examinations showed necrosis and hemorrhages within a large area of the white matter and, to a lesser extent, in the adjacent gray matter, which was centered at the irradiated target. These results indicated that the LINAC system was useful for making brain lesions in experimental animals, while the suitable radiation parameters to generate more focused lesions need to be further explored. We propose the use of a radiosurgical technique for establishing animal models of brain lesions, and discuss the possible uses of this technique for functional neurosurgical treatments in humans.