小鼠局灶性脑缺血后神经症状的时间过程及评价方法

目的：确定我们建立的局灶性脑缺血神经症状定量评价方法的实用性。方法： 大脑中动脉阻塞诱导小鼠局灶性脑缺血后6、12、24 h以及1-7 d，在悬挂试验以计算机视频跟踪技术测定平均角、优势角和转动次数，在爬板试验测定爬板角度；分析定量评价指标与其他行为学评价方法以及脑梗死体积和神经元密度的相关性。结果： 脑缺血后各项定量评价指标均有显著改变，与行为学综合评价的结果相似，6 h的定量评价总分高于12、24 h。缺血后1-7 d内，定量评价总分持续增高，但在3 d后有下降；平均角与相对转动分值在1 d明显增高；爬板角度分值持续增高；经典的神经症状评分则持续增高而无下降。定量评价总分与其他行为学评价以及脑梗死体积和各脑区神经元密度密切相关，其中爬板角度最稳定。结论： 小鼠局灶性脑缺血后12 h至7 d的神经症状稳定，并可逐渐恢复；定量评价方法可提供客观、定量结果，与其他行为学方法及形态学密切相关，其中爬板角度最简便、稳定，可以推广试用。

Time course and evaluation of neurological deficits after focal cerebral ischemia in mice

AIM: To observe time course of neurological deficits after focal cerebral ischemia in mice, and to confirm the quantitative and objective method we developed for evaluating neurological deficits. METHODS: Focal cerebral ischemia was induced by middle cerebral artery occlusion. The neurological deficits were assessed 6 h, 12 h, 24 h, or 1-7 d after ischemia. We measured the mean angles, dominant angles and turns by a computer-assisted video tracking technique in a hanged test, and the holding angles in an inclined plane test. We also analyzed relations between quantitative behavioral assessment and other behavioral assessments, brain infarct volumes, or neuron densities in different brain regions. RESULTS: The behavioral variables measured by the quantitative assessment significantly changed in ischemic mice, similar to those by the complex behavioral assessment, and the total quantitative scores at 6 h after ischemia was higher than those at 12 h and 24 h. During 1-7 d after ischemia, the total quantitative scores had a lasting increase and a tendency of recovery from day 3, the mean angle and relative turn scores markedly increased at day 1, and the holding angle scores persistently increased throughout 7 days. However, the typical neurological scores constantly increased without recovery. Close relations existed between quantitative variables and those of other behavioral assessments, infarct volumes, or neuron densities in different brain regions. Among the quantitative variables, the holding angle was most stable. CONCLUSION: Neurological deficits were stably measured during 12 h to 7 days and recovered gradually in focal cerebral ischemic mice. The quantitative behavioral assessment is useful for getting objective and quantitative data, and holding angle seems to be the simplest and most stable variable for researchers to use in other laboratories.