小鼠控制性脑皮质撞击模型的构建及分级  

The establishment and grading of the controlled cortical impact traumatic brain injury model in mice

作　　者：吴增宝[1] 钟春龙[1] 高阳[1] 刘巧玲[2] 林盈盈[1] 崔振文[1] 郑彦[1] 罗其中[1] 江基尧[1] 

机构地区：[1]上海交通大学医学院附属仁济医院神经外科,上海200127 [2]中国科学院上海高等研究院,上海201210

出　　处：《中华神经外科疾病研究杂志》2013年第5期431-434,共4页Chinese Journal of Neurosurgical Disease Research

基　　金：国家自然科学基金资助项目(30500525;30670719;81070990);上海市科委基金资助项目(09140901300;10QH1401700);上海市教委基金资助项目(09SG20)

摘　　要：目的建立小鼠控制性脑皮质撞击模型,并对损伤程度进行分级,为探索小鼠颅脑创伤的病理生理机制和治疗方法创造条件。方法雄性C57BL/6J小鼠24只,分为4组(实验组3组,对照组1组),每组随机分配6只动物,应用PinPointTMPCI3000精细颅脑撞击仪,设定不同的打击参数,精确撞击小鼠脑皮质。其中,实验组打击深度分别为0.5 mm、1.0 mm、1.5 mm;打击时间均为80 ms;打击速度均为1.5 m/s。对照组只开骨窗,不打击脑皮质。致伤后观察小鼠意识和神经反射的抑制时间。伤后24h处死小鼠,取脑组织行HE染色,Fluoro-Jade B组织荧光染色。观察小鼠脑组织损伤侧海马CA3区退变神经元数目的变化。结果小鼠的脑损伤程度和打击强度相关;打击深度为0.5mm时模拟轻度颅脑损伤;打击深度为1.0 mm时模拟中度颅脑损伤;打击深度为1.5 mm时模拟重度颅脑损伤。结论应用PinPointTMPCI3000精细颅脑撞击仪成功创建出小鼠控制性脑皮质撞击模型,并且给予轻度、中度、重度损伤分级,为进一步研究颅脑创伤病理生理机制和治疗方法创造条件。Objective To establish the controlled cortical impact traumatic brain injury model in mice and dictate grading of deficits. This model may serve as a suitable platform with which to explore pathophysiology to traumatic brain injury and ultimately the development of novel, effective therapeutics. Methods A total of 24 male C57BL/6J mice were divided into 4 groups, experimental groups （ 3 groups） and sham group （ 1 group）, respectively. There were 6 animals in each group. The controlled cortical impact device impacted the brain at a velocity of 1.5 m/s reaching a depth of 0.5 mm, 1.0 mm or 1.5 mm for mild, moderate and severe traumatic brain injury （TBI） model, respectively, below the dura matter layer and remained in the brain for 80 ms. Sham injury group consisted of animals exposed to eranieetomy and suturing. The suppression duration of consciousness and neurological reflex were used as an indicator of traumatic brain injury severity. Mice were euthartized at 24 h after impacted and brains were processed and stained according to the HE staining and Flouro-Jade B histofluorescence staining. Ipsilateral neuronal degeneration in the CA3 regions of the hippocampns was quantified using stereologieal techniques. Results The severity of the pathological changes in mice was increased as the injury aggravated. The PinPointTM ~ precision cortical impactor device impacted the brain at a depth of 0.5 mm, 1.0 mm or 1.5 mm for mild, moderate and severe TBI model, respectively. Conclusion The PinPointTM PCI3000 precision cortical impactor device produces graded cortical impact injury in mice successfully. The development of a TBI model in mice will facilitate investigations into the molecular pathways underlying the pathophysiology and treatment of the trauma.

关 键 词：颅脑创伤 控制性脑皮质撞击 Fluoro—Jade B组织荧光染色 动物模型 

分 类 号：R741[医药卫生—神经病学与精神病学]