Abstract:

Objective To establish a stable mouse cerebral ischemia model of distal middle cerebral artery (MCA) thrombosis induced by ferric chloride, and evaluate the severity of neurological deficit after cerebral ischemic injury. Methods C57BL6/J male mice were randomly divided into cerebral ischemia group and sham group. In cerebral ischemia group, 10% ferric chloride solution was used to induce thrombosis in right distal MCA. Right cerebral and MCA blood flow were measured before operation, 10 minutes after operation, day 1 and 7 after operation. TTC staining was used to evaluate cerebral infarction on day 1 after operation. Three neurological scores (mGS, mNSS and NES) and adhesive removal test were used to evaluate neurological function deficit of mice on day 1, 3, 5 and 7 after operation. On day 7, neuronal nuclei were observed by immunofluorescence staining to evaluate cerebral injury, and CD16/32, CD206 and Iba1 were stained to evaluate glial cells expression. Results Compared to sham group, the following changes occurred in ischemia group: right cerebral blood flow and MCA blood flow all decreased at 10 minutes, day 1 and 7 after operation; obvious cerebral infarction occurred on day 1 after operation and persisted on day 7; three neurological scores and adhesive removal test all indicated different degrees of neurological impairment of mice in ischemia group; the expression of M1 and M2 glial cells around cerebral infarction increased on day 7. Conclusions A stable mouse cerebral ischemia model can be established by using Ferric chloride solution. The following changes can be observed in mouse models: the cerebral blood flow and MCA blood flow on surgical side decreased; cerebral cortex infarct and neurological function deficit appeared; the expression of glial cells around the infarction up-regulated.

Key words: Cerebral ischemia model; Ferric chloride; Thrombosis; Middle cerebral artery

摘要：

目的 建立稳定的小鼠大脑中动脉远端氯化铁血栓模型，评价其造成的脑损伤及神经功能损伤程 度。 方法 C57BL6/J雄性小鼠随机分为脑缺血组和假手术组。脑缺血组用10%氯化铁（ferric chloride， FeCl3）溶液诱导右侧大脑中动脉远端形成血栓。在术前、术后10 mi n、术后1 d和7 d观测术侧脑血流 和手术动脉血流量的变化。术后1 d观察脑组织梗死率。术后1 d、3 d、5 d、7 d用3种神经学评分[改良 加西亚评分（modified Garcia score，mGS）、改良神经损伤严重程度评分（modified neurological severity scores，mNSS）和15分神经学评估表（15-point neurological evaluation scale，NES）]和胶黏纸测试评价小 鼠神经功能。术后7 d免疫荧光染色标记神经细胞核观察脑组织损伤，标记CD16/32、CD206和Iba1观 察胶质细胞表达。 结果 与假手术组相比，脑缺血组术后10 mi n、1 d、7 d脑表面血流和手术动脉血流下降，术后1 d脑 皮层梗死明显，术后7 d仍有明显脑组织损伤；脑缺血组术后1 d、3 d、5 d和7 d时3种神经学评分及胶 黏纸测试均提示小鼠神经功能不同程度损伤。术后7 d脑缺血组梗死周围皮层M1和M2型胶质细胞表 达增加。 结论 FeCl3溶液可诱导形成稳定的小鼠脑缺血模型，该模型可造成手术侧大脑中动脉远端及脑表 面血流量降低，皮层脑梗死，小鼠神经功能受损，梗死周围胶质细胞表达上调。本研究建立了稳定 氯化铁诱导血栓形成的小鼠脑缺血模型，为脑血栓形成和抗栓药物治疗提供了一种可靠的研究工 具。

关键词: 脑缺血模型; 氯化铁; 血栓; 大脑中动脉