A MODEL OF PARASAGITTAL CONTROLLED CORTICAL IMPACT IN THE MOUSE - COGNITIVE AND HISTOPATHOLOGIC EFFECTS
A MODEL OF PARASAGITTAL CONTROLLED CORTICAL IMPACT IN THE MOUSE - COGNITIVE AND HISTOPATHOLOGIC EFFECTS
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DOI：
10.1089/neu.1995.12.169
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发表时间：
1995-04-01
影响因子：
4.2
通讯作者：
MCINTOSH, TK
中科院分区：
文献类型：
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作者：
SMITH, DH;SOARES, HD;MCINTOSH, TK
控制性皮质冲击（CCI）是一种使用气动冲击器产生创伤性脑损伤的方法，以前在雪貂和大鼠中都有过研究。在本研究中，我们应用该技术建立了另一物种小鼠脑损伤的CCI模型，并对其进行了表征，评估了认知和组织病理学结果。在麻醉（戊巴比妥钠，65 mg/kg）的雄性C57BL小鼠中，我们使用直径为3 mm的圆头诱捕器，在左侧顶叶皮层（副矢状面）上方，以5.7-6.2 m/s的速度和1 mm的深度对其进行假治疗（无损伤，n = 12）或CCI损伤（n = 12）。在这种程度的损伤下，我们观察到损伤后2天Morris水迷宫任务的记忆保留有非常显著的缺陷（p < 0.001）。在损伤后48小时进行的死后组织病理学分析显示，在撞击区域有大量的皮质组织丢失，并且在CA2， CA3和CA3c区域有选择性的海马神经元细胞丢失。使用改良的galyas银染色技术对退化的神经元进行分析，结果表明，在与撞击部位相邻的皮质和同侧海马齿状回中，神经元的损伤是一致的。沿胼胝体的灰质-白质界面可见双侧变性。神经胶质原纤维酸性蛋白（GFAP）免疫组化显示，损伤后48小时，双侧皮质、海马和丘脑出现广泛的反应性胶质细胞增生。抗小鼠IgG免疫组化证实了血脑屏障的破坏，显示内源性IgG在同侧皮质、海马和丘脑外渗。这些结果表明，这种新的小鼠旁矢状面CCI模型模拟了在其他啮齿动物的先前表征的脑损伤模型中观察到的许多成熟的后遗症。这种小鼠模型可能是一种特别有用的实验工具，用于比较野生型和转基因小鼠的外伤性脑损伤的行为和组织病理学特征。
Controlled cortical impact (CCI), using a pneumatically driven impactor to produce traumatic brain injury, has been characterized previously in both the ferret and in the rat. In the present study, we applied this technique to establish and characterize the CCI model of brain injury in another species, the mouse, evaluating cognitive and histopathologic outcome. In anesthetized (sodium pentobarbital, 65 mg/kg) male C57BL mice, we performed sham treatment (no injury, n = 12) or CCI injury (n = 12) at a velocity of 5.7-6.2 m/sec and depth of 1 mm, using a 3-mm diameter rounded-tip impounder, positioned over the left parietotemporal cortex (parasagittal). At this level of injury, we observed highly significant deficits in memory retention of a Morris water maze task 2 days following injury (p < 0.001). Postmortem histopathologic analysis performed at 48 h following injury revealed substantial cortical tissue loss in the region of impact and selective hippocampal neuronal cell loss in the CA2, CA3, and CA3c regions, using Nissl staining. Analysis of degenerating neurons using modified Gallyas silver staining techniques demonstrated consistent ipsilateral injury of neurons in the cortex adjacent to the impact site and in the dentate gyrus of the ipsilateral hippocampus. Bilateral degeneration was observed at the gray matter-white matter interface along the corpus callosum. Glial fibrillary acidic protein (GFAP) immunohistochemistry revealed extensive reactive gliosis appearing diffusely through the bilateral cortices, hippocampi, and thalami at 48 h postinjury. Breakdown of the blood-brain barrier was demonstrated with antimouse IgG immunohistochemistry, revealing extravasation of endogenous IgG throughout the ipsilateral cortex, hippocampus, and thalamus. These results suggest that this new model of parasagittal CCI in the mouse mimics a number of well-established sequelae observed in previously characterized brain injury models using other rodent species. This mouse model may be a particularly useful experimental tool for comparing behavioral and histopathologic characteristics of traumatic brain injury in wild-type and genetically altered mice.