Thompson Hilaire J, LeBold David G, Marklund Niklas, Morales Diego M, Hagner Andrew P, McIntosh Tracy K
Traumatic Brain Injury Laboratory, Department of Neurosurgery, The University of Pennsylvania, Philadelphia, PA, USA.
Restor Neurol Neurosci. 2006;24(2):109-14.
As deficits in memory and cognition are commonly observed in survivors of traumatic brain injury (TBI), causing reduced quality of life for the patient, a major goal in experimental TBI research is to identify and evaluate cognitive dysfunction. The present study assessed the applicability of the serial Morris water maze (MWM) test to determine cognitive function following experimental TBI in the same group of rats which is particularly important for long-term studies and increasingly valuable for the evaluation of novel treatment strategies.
Male Sprague-Dawley rats (n = 27) were anesthetized and subjected to either sham injury (n = 9) or lateral fluid percussion (FP) brain injury of moderate severity (n = 18). At 4 weeks post-injury, animals were trained in a water maze over 3 days (acquisition/learning phase) to find a submerged platform. At 8 weeks post-injury the hidden platform was then moved to the opposite quadrant, and animals were trained to find the new position of the platform over 3 days. Forty-eight hours later, animals were tested for memory retention in a probe trial in which the platform was not present.
Brain-injured animals had significant learning impairment (p < 0.0001), shifted-learning impairment (p < 0.001) and memory retention deficits (p < 0.01) in comparison to their sham-injured counterparts over the 8 week testing period. Swim speed and distance were not significantly altered by brain injury at any time point.
The validation of this testing paradigm using a clinically relevant experimental brain injury model is an important addition to behavioral outcome testing.
由于创伤性脑损伤(TBI)幸存者中普遍存在记忆和认知缺陷,导致患者生活质量下降,因此实验性TBI研究的一个主要目标是识别和评估认知功能障碍。本研究评估了连续莫里斯水迷宫(MWM)测试在同一组大鼠实验性TBI后确定认知功能的适用性,这对于长期研究尤为重要,对于评估新的治疗策略也越来越有价值。
将雄性Sprague-Dawley大鼠(n = 27)麻醉,分别进行假损伤(n = 9)或中度严重程度的侧方液体冲击(FP)脑损伤(n = 18)。在损伤后4周,动物在水迷宫中训练3天(获取/学习阶段)以找到一个水下平台。在损伤后8周,将隐藏平台移至相对象限,动物再训练3天以找到平台的新位置。48小时后,在平台不存在的探测试验中测试动物的记忆保持能力。
在8周的测试期内,与假损伤的动物相比,脑损伤动物存在显著的学习障碍(p < 0.0001)、转换学习障碍(p < 0.001)和记忆保持缺陷(p < 0.01)。在任何时间点,脑损伤均未显著改变游泳速度和距离。
使用临床相关的实验性脑损伤模型对该测试范式进行验证,是行为结果测试的一项重要补充。