Stroke is a leading cause of death and disability in the United States. Most strokes are ischemic, resulting in both cognitive and motor impairments. Animal models of ischemic stroke such as the distal middle cerebral artery occlusion (dMCAO) and photothrombotic stroke (PTS) procedures have become invaluable tools, with their own advantages and disadvantages. The dMCAO model is clinically relevant as it occludes the artery most affected in humans, but yields variability in the infarct location as well as the behavioral and cognitive phenotypes disrupted. The PTS model has the advantage of allowing for targeted location of infarct, but is less clinically relevant. The present study evaluates phenotype disruption over time in mice subjected to either dMCAO, PTS, or a sham surgery. Post-surgery, animals were tested over 28 days on standard motor tasks (grid walk, cylinder, tapered beam, and rotating beam), as well as a novel odor-based operant task; the 5:1 Odor Discrimination Task (ODT). Results demonstrate a significantly greater disturbance of motor control with PTS as compared with Sham and dMCAO. Disruption of the PTS group was detected up to 28 days post-stroke on the grid walk, and up to 7 days on the rotating and tapered beam tasks. PTS also led to significant short-term disruption of ODT performance (1-day post-surgery), exclusively in males, which appeared to be driven by motoric disruption of the lick response. Together, this data provides critical insights into the selection and optimization of animal models for ischemic stroke research. Notably, the PTS procedure was best suited for producing disruptions of motor behavior that can be detected with common behavioral assays and are relatively enduring, as is observed in human stroke.

中文翻译：

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两种常用中风动物模型检测缺陷的灵敏度提高

中风是美国死亡和残疾的主要原因。大多数中风是缺血性的，导致认知和运动障碍。缺血性中风的动物模型，例如远端大脑中动脉闭塞（dMCAO）和光血栓性中风（PTS）手术已成为宝贵的工具，各有其优点和缺点。 dMCAO 模型具有临床相关性，因为它会闭塞人类受影响最严重的动脉，但会产生梗塞位置的变异性以及行为和认知表型的破坏。 PTS 模型的优点是可以确定梗塞的目标位置，但临床相关性较低。本研究评估了接受 dMCAO、PTS 或假手术的小鼠随时间的表型破坏。手术后，动物接受了为期 28 天的标准运动任务（网格行走、圆柱、锥形梁和旋转梁）以及基于气味的新颖操作任务的测试； 5:1 气味辨别任务 (ODT)。结果表明，与 Sham 和 dMCAO 相比，PTS 对运动控制的干扰明显更大。在中风后 28 天的网格行走中检测到 PTS 组的中断，在旋转和锥形梁任务中检测到 7 天的 PTS 组中断。 PTS 还导致 ODT 表现（术后 1 天）出现严重的短期破坏，这种情况仅发生在雄性中，这似乎是由舔反应的运动破坏引起的。总之，这些数据为缺血性中风研究动物模型的选择和优化提供了重要的见解。值得注意的是，PTS 程序最适合产生运动行为的干扰，这种干扰可以通过常见的行为分析检测到，并且相对持久，正如在人类中风中观察到的那样。