From the Department of Neurology, University of Münster, Münster, Germany (A.S., K.D., J.-K.S., B.G., M.H., T.D., J.M.); and Department of Neurology, Bethel-EvKB, Bielefeld, Germany (W.-R.S.).
Stroke. 2015 Apr;46(4):1127-31. doi: 10.1161/STROKEAHA.115.008905. Epub 2015 Mar 5.
In spite of its high disease burden, there is no specific treatment for multi-infarct dementia. The preclinical evaluation of candidate drugs is limited because an appropriate animal model is lacking. Therefore, we aimed to evaluate whether a mouse model of recurrent photothrombotic stroke is suitable for the preclinical investigation of multi-infarct dementia.
Recurrent photothrombotic cortical infarcts were induced in 25 adult C57BL/6 mice. Twenty-five sham-operated animals served as controls. The object recognition test and the Morris water maze test were performed >6 weeks to assess cognitive deficits. Afterward, histological analyses were performed to characterize histopathologic changes associated with recurrent photothrombotic infarcts.
After the first infarct, the object recognition test showed a trend toward an impaired formation of recognition memories (P=0.08), and the Morris Water Maze test revealed significantly impaired spatial learning and memory functions (P<0.05). After recurrent infarcts, the object recognition test showed significant recognition memory deficits (P<0.001) and the Morris water maze test demonstrated persisting spatial learning and memory deficits (P<0.05). Histological analyses revealed remote astrogliosis in the hippocampus.
Our results show progressive cognitive deficits in a mouse model of recurrent photothrombotic stroke. The presented model resembles the clinical features of human multi-infarct dementia and enables the investigation of its pathophysiological mechanisms and the evaluation of treatment strategies.
尽管多发性脑梗死性痴呆的疾病负担很高，但目前尚无针对该疾病的特异性治疗方法。由于缺乏合适的动物模型，候选药物的临床前评估受到限制。因此，我们旨在评估反复光血栓性皮质梗死小鼠模型是否适合用于多发性脑梗死性痴呆的临床前研究。
在 25 只成年 C57BL/6 小鼠中诱导反复光血栓性皮质梗死。25 只假手术对照动物作为对照组。在 >6 周后进行物体识别测试和 Morris 水迷宫测试，以评估认知功能障碍。随后进行组织学分析，以描述与反复光血栓性梗死相关的组织病理学变化。
首次梗死后，物体识别测试显示识别记忆形成趋势受损（P=0.08），Morris 水迷宫测试显示空间学习和记忆功能显著受损（P<0.05）。反复梗死后，物体识别测试显示出明显的识别记忆缺陷（P<0.001），Morris 水迷宫测试显示出持续的空间学习和记忆缺陷（P<0.05）。组织学分析显示海马区存在远隔性星形胶质增生。
我们的研究结果显示，反复光血栓性卒中小鼠模型存在进行性认知缺陷。该模型类似于人类多发性脑梗死性痴呆的临床特征，可用于研究其病理生理学机制和评估治疗策略。
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