Establishment of Early Endpoints in Mouse Total-Body Irradiation Model.
Establishment of Early Endpoints in Mouse Total-Body Irradiation Model.
复制标题
DOI：
10.1371/journal.pone.0161079
复制
发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Ossetrova N
中科院分区：
文献类型：
--
作者：
Koch A;Gulani J;King G;Hieber K;Chappell M;Ossetrova N
电离辐射后的急性放射病(ARS)以辐射引起的多器官功能障碍/衰竭为特征，指的是两个或多个器官系统的进行性功能障碍，其病因是随着时间的推移对细胞和组织的辐射损伤。人类和动物的辐射敏感性数据使描述与ARS相关的迹象成为可能。先前已经建立了一种全身照射(TBI)的小鼠模型，该模型代表了人类人口中可能发生的照射情景。在这里，我们介绍了由武装部队放射生物学研究所兽医学系开发的小鼠干预评分系统(MISH)，以识别死亡的小鼠并减少发现死亡的小鼠的数量，因此这是一种更人性化的以死亡为终点的改进。在小鼠(CD2F1雄性)脑损伤模型(6-14Gy60Coγ射线0.6Gymin-1)中，将存活率与体重和温度的变化进行比较，这为评分系统的改进提供了依据。通过植入的微芯片对动物进行个体跟踪，可以根据个人而不是群体平均水平来评估标准。在总共132只小鼠(92只受到辐射)中，51只小鼠被实施了安乐死，而只有4只小鼠被发现死亡(占死亡人数的7%)。在这种情况下，在两次观察之间的一夜时间后，所有四只老鼠都被发现死亡。体重减轻本身就预示着即将死于辐射损伤，然而，在体重减轻30%的情况下，小鼠并不总是在24小时内死亡。只有一名幸存者体重减轻了30%以上。在10GY和14GY动物中，死亡/安乐死前2-4天的体温显著下降。与使用发病率或死亡率的主观评估作为这些生存研究的终点相比，评分系统显示出显著的改进。
Acute radiation sickness (ARS) following exposure to ionizing irradiation is characterized by radiation-induced multiorgan dysfunction/failure that refers to progressive dysfunction of two or more organ systems, the etiological agent being radiation damage to cells and tissues over time. Radiation sensitivity data on humans and animals has made it possible to describe the signs associated with ARS. A mouse model of total-body irradiation (TBI) has previously been developed that represents the likely scenario of exposure in the human population. Herein, we present the Mouse Intervention Scoring System (MISS) developed at the Veterinary Sciences Department (VSD) of the Armed Forces Radiobiology Research Institute (AFRRI) to identify moribund mice and decrease the numbers of mice found dead, which is therefore a more humane refinement to death as the endpoint. Survival rates were compared to changes in body weights and temperatures in the mouse (CD2F1 male) TBI model (6–14 Gy, 60Co γ-rays at 0.6 Gy min-1), which informed improvements to the Scoring System. Individual tracking of animals via implanted microchips allowed for assessment of criteria based on individuals rather than by group averages. From a total of 132 mice (92 irradiated), 51 mice were euthanized versus only four mice that were found dead (7% of non-survivors). In this case, all four mice were found dead after overnight periods between observations. Weight loss alone was indicative of imminent succumbing to radiation injury, however mice did not always become moribund within 24 hours while having weight loss >30%. Only one survivor had a weight loss of greater than 30%. Temperature significantly dropped only 2–4 days before death/euthanasia in 10 and 14 Gy animals. The score system demonstrates a significant refinement as compared to using subjective assessment of morbidity or death as the endpoint for these survival studies.
登录
查看更多内容
影响因子：
2.2
作者：
Farese AM;Cohen MV;Katz BP;Smith CP;Jackson W 3rd;Cohen DM;MacVittie TJ
通讯作者：
MacVittie TJ
影响因子：
3.7
作者：
Layton RC;Gigliotti A;Armijo P;Myers L;Knight J;Donart N;Pyles J;Vaughan S;Plourde J;Fomukong N;Harrod KS;Gao P;Koster F
通讯作者：
Koster F
影响因子：
2.2
作者：
Booth C;Tudor G;Tudor J;Katz BP;MacVittie TJ
通讯作者：
MacVittie TJ
影响因子：
5.5
作者：
Shang, Shaobin;Shanley, Crystal A.;Basaraba, Randall J.
通讯作者：
Basaraba, Randall J.
影响因子：
3.4
作者：
Satyamitra, Merriline;Lombardini, Eric;Srinivasan, Venkataraman
通讯作者：
Srinivasan, Venkataraman