一种模拟大鼠不同程度颅脑损伤模型的构建与评估

A new model of traumatic brain injury with varying degree of severity in rats

目的构建并评估可以模拟不同损伤程度的大鼠颅脑损伤模型。方法将12只大鼠随机分为3组(轻、中、重度颅脑损伤组),以可控性颅脑损伤模型为基础,不同组采用特定致伤参数(探头致伤深度:轻度为2~3 mm,中度为3~4 mm,重度为4~5 mm;致伤速度均为2.5 m/s,致伤时间为0.1 s),造成不同程度颅脑损伤。分别采用MRI、行为学定量评价,颅脑病理定性分析,评估颅脑损伤程度。结果损伤后大鼠均出现不同程度行为异常,损伤颅脑病理显示组织神经元减少,小胶质细胞浸润,不同程度充血、水肿,轻度颅脑损伤组损伤体积(11.33±1.11)mm^3,中度颅脑损伤组损伤体积(20.77±1.90)mm^3,重度颅脑损伤组损伤体积(46.19±12.79)mm^3。结论采用可控性颅脑损伤方法可构建具有良好重复性、可靠性、稳定性的大鼠颅脑损伤模型,多种方式定量评估损伤程度相对精确,为后续研究奠定了基础。

Objective To establish and evaluate traumatic brain injury model with varying degrees in rats. Methods Twelve rats were randomly divided into three groups（mild group, moderate group, severe group）. Controlled cortical impact（CCI） device was used to cause brain injury in rat model by different impact heads（mild group： diameter = 2 mm, moderate group： diameter = 2.5 mm, severe group： diameter = 3 mm） and different impact depth（mild group： 2-3 mm, moderate group： 3-4 mm, severe group： 4-5 mm） with impact duration of 0.1 s and impact velocity of 2.5 m/s. After modeling, brain histopathology changes were observed to make sure if modeling was successful. Magnetic resonance imaging（MRI） scan was performed and the Revised Neurobehavioral Severity Scale（NSS-R） was used to evaluate the extent of brain injury of three groups accurately. Results After modeling, all rats showed abnormal behaviors. In the damaged regions, the number of neuron decreased, with diffusive infiltration of microglia, congestion, vacuolar degeneration in various cells. The total volume of injury brain of mild group was（11.33±1.11） mm3,（20.77±1.90） mm3 in moderate group and（46.19±12.79） mm3 in severe group. Conclusion Traumatic brain injury models with varying degree of severity are established successfully in rats by application of CCI device, and the degree of injury is assessed by different methods with quantifiable, stable and repeatable results, which can be the groundwork for further study.