Department of Anesthesiology and the Center for Shock, Trauma, and Anesthesiology Research (STAR), University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
J Neurotrauma. 2012 Oct 10;29(15):2475-89. doi: 10.1089/neu.2012.2511. Epub 2012 Aug 27.
Controlled cortical impact injury (CCI) is a widely-used, clinically-relevant model of traumatic brain injury (TBI). Although functional outcomes have been used for years in this model, little work has been done to compare the predictive value of various cognitive and sensorimotor assessment tests, singly or in combination. Such information would be particularly useful for assessing mechanisms of injury or therapeutic interventions. Following isoflurane anesthesia, C57BL/6 mice were subjected to sham, mild (5.0 m/sec), moderate (6.0 m/sec), or severe (7.5 m/sec) CCI. A battery of behavioral tests were evaluated and compared, including the standard Morris water maze (sMWM), reversal Morris water maze (rMWM), novel object recognition (NOR), passive avoidance (PA), tail-suspension (TS), beam walk (BW), and open-field locomotor activity. The BW task, performed at post-injury days (PID) 0, 1, 3, 7, 14, 21, and 28, showed good discrimination as a function of injury severity. The sMWM and rMWM tests (PID 14-23), as well as NOR (PID 24 and 25), effectively discriminated spatial and novel object learning and memory across injury severity levels. Notably, the rMWM showed the greatest separation between mild and moderate/severe injury. PA (PID 27 and 28) and TS (PID 24) also reflected differences across injury levels, but to a lesser degree. We also compared individual functional measures with histological outcomes such as lesion volume and neuronal cell loss across anatomical regions. In addition, we created a novel composite behavioral score index from individual complementary behavioral scores, and it provided superior discrimination across injury severities compared to individual tests. In summary, this study demonstrates the feasibility of using a larger number of complementary functional outcome behavioral tests than those traditionally employed to follow post-traumatic recovery after TBI, and suggests that the composite score may be a helpful tool for screening new neuroprotective agents or for addressing injury mechanisms.
皮质控制冲击损伤（CCI）是一种广泛使用的、与临床相关的创伤性脑损伤（TBI）模型。尽管该模型多年来一直使用功能结果，但很少有工作比较各种认知和感觉运动评估测试的预测价值，无论是单独使用还是组合使用。此类信息对于评估损伤机制或治疗干预措施将特别有用。在异氟烷麻醉后，C57BL/6 小鼠接受假手术、轻度（5.0m/sec）、中度（6.0m/sec）或重度（7.5m/sec）CCI。评估并比较了一系列行为测试，包括标准莫里斯水迷宫（sMWM）、反转莫里斯水迷宫（rMWM）、新物体识别（NOR）、被动回避（PA）、悬尾（TS）、横梁行走（BW）和旷场运动活动。BW 任务在损伤后第 0、1、3、7、14、21 和 28 天进行，表现出良好的损伤严重程度差异识别能力。sMWM 和 rMWM 测试（损伤后第 14-23 天）以及 NOR（损伤后第 24 和 25 天）有效区分了不同损伤严重程度的空间和新物体学习和记忆。值得注意的是，rMWM 显示出轻度和中度/重度损伤之间最大的分离。PA（损伤后第 27 和 28 天）和 TS（损伤后第 24 天）也反映了不同损伤水平之间的差异，但程度较小。我们还比较了个体功能测量值与组织学结果，如损伤体积和神经元细胞丢失，横跨解剖区域。此外，我们根据单个互补行为评分创建了一个新的综合行为评分指数，与单个测试相比，它在不同损伤严重程度下提供了更好的区分度。总之，这项研究表明，使用比传统方法更多的互补功能结果行为测试来跟踪 TBI 后的创伤后恢复是可行的，并且表明综合评分可能是筛选新神经保护剂或解决损伤机制的有用工具。
