Semmler Alexander, Garbe Stephan, Moskau Susanna, Frisch Christian, Eter Nicole, Schlegel Uwe, Linnebank Michael
Department of Neurology, University Zurich, Switzerland.
Neurol Res. 2013 May;35(4):355-9. doi: 10.1179/1743132812Y.0000000143. Epub 2013 Jan 10.
In order to test for mechanisms of whole brain radio therapy side effects and possible neuroprotective measures, a rodent model is desirable. In many models, a high single dose of 8-20 Gray (Gy) of whole brain irradiation is used. These experimental radiation protocols do not closely reflect the clinical situation, where the cumulative dosage is applied in smaller fractions. We describe an efficient method to perform repetitive, fractionated whole brain radio therapy to the rat brain.
Fifteen-week-old rats were irradiated with a dose of 5 or 10 Gy on four consecutive days, resulting in a cumulative dose in opposing fields of 20 Gy (n = 15) and 40 Gy (n = 17), respectively. Sham-irradiated rats (n = 14) received the same procedure but without application of cranial irradiation. Four collimators with a diameter of 3 cm each were used to place four rats and an ionization chamber simultaneously in the dose field for monitoring.
Fourteen days after the procedure, irradiated animals showed decreased open-field activity (two-tailed t-test, sham versus 20 Gy, P<0.001; sham versus 40 Gy, P = 0.002), but no cognitive deficit as indicated by latencies in the Morris water maze test. Six weeks after the irradiation, no group showed alterations of histopathology such as vascular changes, demyelination, or white matter necrosis.
The proposed model represents an efficient and safe method to perform fractioned high-dose irradiation of the rodent brain. Speculatively, it is possible to increase the cumulative dosage and dose per fraction used in this model to achieve a higher degree of radiation-induced toxicity.
为了测试全脑放射治疗副作用的机制以及可能的神经保护措施，需要一种啮齿动物模型。在许多模型中，使用单次高剂量8 - 20格雷（Gy）的全脑照射。这些实验性放射方案并不能紧密反映临床情况，临床中累积剂量是以较小分次给予的。我们描述了一种对大鼠脑进行重复性、分次全脑放射治疗的有效方法。
15周龄大鼠连续4天接受5或10 Gy的照射，在相对野中累积剂量分别为20 Gy（n = 15）和40 Gy（n = 17）。假照射大鼠（n = 14）接受相同操作，但不进行颅脑照射。使用四个直径为3 cm的准直器将四只大鼠和一个电离室同时置于剂量场中进行监测。
照射后14天，照射动物的旷场活动减少（双尾t检验，假照射组与20 Gy组比较，P<0.001；假照射组与40 Gy组比较，P = 0.002），但在莫里斯水迷宫试验中潜伏期未显示出认知缺陷。照射后6周，各组均未出现组织病理学改变，如血管变化、脱髓鞘或白质坏死。
所提出的模型是一种对啮齿动物脑进行分次高剂量照射的有效且安全的方法。推测有可能增加该模型中使用的累积剂量和分次剂量，以实现更高程度的辐射诱导毒性。
