Shibata Masunari, Yamasaki Nobuyuki, Miyakawa Tsuyoshi, Kalaria Rajesh N, Fujita Youshi, Ohtani Ryo, Ihara Masafumi, Takahashi Ryosuke, Tomimoto Hidekazu
Department of Neurology, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan.
Stroke. 2007 Oct;38(10):2826-32. doi: 10.1161/STROKEAHA.107.490151. Epub 2007 Aug 30.
We recently designed a mouse model of chronic cerebral hypoperfusion, in which the cerebral white matter is damaged without significant gray matter lesions. The behavioral characteristics of these mice were studied using a test battery for neurological and cognitive functions.
Adult C57Bl/6 male mice were subjected to either sham-operation or bilateral common carotid artery stenosis (BCAS) using microcoils with an internal diameter of 0.18 mm. At 30 days after BCAS, 70 animals were divided into 3 groups and subjected to behavioral test batteries. The first group underwent comprehensive behavioral test, including the neurological screen, prepulse inhibition, hot plate, open field, light/dark transition, Porsolt forced swim and contextual and cued fear conditioning (BCAS n=13; sham-operated n=11). The second group was for the working memory task of the 8-arm radial maze test (BCAS n=12; sham-operated n=10), and the third for the reference memory task of the 8-arm radial maze test (BCAS n=13; sham-operated n=11). Another batch of animals were examined for histological changes (BCAS n=11; sham-operated n=12).
The white matter including the corpus callosum was consistently found to be rarefied without clear ischemic lesions in the hippocampus. No apparent differences were observed in the comprehensive test batteries between the control and BCAS mice. However, in the working memory tasks tested with the 8-arm radial maze, the BCAS mice made significantly more errors than the control mice (P<0.0001). Again, there were no detectable differences in the reference memory tasks between the groups.
At 30 days after BCAS, working memory deficits as well as white matter changes were apparent in the mice. Working memory deficit was attributable to damage of the frontal-subcortical circuits, suggesting the BCAS model is useful to evaluate the substrates of subcortical vascular dementia.
我们最近设计了一种慢性脑灌注不足的小鼠模型，在该模型中脑白质受损而灰质无明显病变。使用一套神经和认知功能测试对这些小鼠的行为特征进行了研究。
成年C57Bl/6雄性小鼠接受假手术或使用内径为0.18 mm的微线圈进行双侧颈总动脉狭窄（BCAS）手术。BCAS术后30天，将70只动物分为3组并进行行为测试。第一组进行全面行为测试，包括神经学筛查、前脉冲抑制、热板试验、旷场试验、明暗转换试验、波索尔特强迫游泳试验以及情境和线索恐惧条件反射试验（BCAS组n = 13；假手术组n = 11）。第二组用于八臂放射状迷宫试验的工作记忆任务（BCAS组n = 12；假手术组n = 10），第三组用于八臂放射状迷宫试验的参考记忆任务（BCAS组n = 13；假手术组n = 11）。另一批动物用于检查组织学变化（BCAS组n = 11；假手术组n = 12）。
始终发现包括胼胝体在内的白质稀疏，海马体无明显缺血性病变。在对照小鼠和BCAS小鼠之间的综合测试中未观察到明显差异。然而，在用八臂放射状迷宫测试的工作记忆任务中，BCAS小鼠比对照小鼠犯的错误明显更多（P < 0.0001）。同样，两组之间在参考记忆任务中未检测到差异。
BCAS术后30天，小鼠出现工作记忆缺陷以及白质变化。工作记忆缺陷归因于额叶 - 皮质下回路的损伤，表明BCAS模型可用于评估皮质下血管性痴呆的发病机制。
Zotero 插件