Adaptation of the fluid percussion injury model to the mouse

Adaptation of the fluid percussion injury model to the mouse
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DOI:
10.1089/neu.1998.15.217
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发表时间:
1998-03-01
影响因子:
4.2
通讯作者:
Grady, MS
Grady, MS
中科院分区:
医学2区
文献类型:
--
作者:
Carbonell, WS;Maris, DO;Grady, MS

文献摘要

被引文献

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流体冲击伤(FPI)是大鼠创伤性脑损伤(TBI)的一种典型实验模型。脑外伤后的许多病理生理后果和恢复机制依赖于可以在基因改变的小鼠中检测到的神经化学途径。因此,应用于小鼠的FPI可能是在分子水平上研究脑损伤的有用的实验工具。在本研究中,我们通过描述急性神经学、组织病理学和行为学的变化,在小鼠中建立了一种可行的脑外伤模型。雄性C57BL/6小鼠接受右侧矢状面旁照射或假手术治疗。急性神经学评估显示,受伤的动物有翻正反射(p<0.001)。Morris水迷宫(MWM)大鼠分别于损伤后5d和6d出现空间学习记忆障碍。描述了一种新的MWM数据分析协议。与假动物(n=16)相比,损伤组(n=18)在获取(p<0.025)和探查试验(p<0.025)中表现出在MWM中的表现受损。在损伤后7天,胶质纤维酸性蛋白免疫组织化学显示皮质、胼胝体和海马区胶质细胞明显增多。改良的Galyas银染色法一致地标记了同侧脑皮质的胞体和终末,双侧痂体内灰质-白质交界处的轴突,以及双侧丘脑的终末和纤维。此外,所描述的小鼠FPI模型可以立即用于已经使用FPI大鼠模型的实验室,而不需要对现有的PPI设备进行修改。
Fluid percussion injury (FPI) is a well-characterized experimental model of traumatic brain injury (TBI) in the rat. Many pathophysiologic consequences and mechanisms of recovery after TBI rely on neurochemical pathways that can be examined in genetically altered mice. Therefore, FPI applied to mice may be a useful experimental tool to investigate TBI at the molecular level. In the present study, we establish FPI as a viable model of TBI in the mouse by characterizing acute neurological, histopathological, and behavioral changes. Right-sided parasagittal FPI or sham treatment was administered in male C57BL/6 mice. Acute neurological evaluation revealed righting reflexes in the injured animals (p < 0.001). Deficits in spatial learning and memory were observed in the Morris water maze (MWM) 5 and 6 days after injury. A novel MWM data analysis protocol is described. The injured group (n = 18) demonstrated impaired performance in the MWM during acquisition (p < 0.05) and probe trials (p < 0.025) compared to sham animals (n = 16). At 7 days postinjury, glial fibrillary acidic protein immunohistochemistry revealed intense cortical, callosal, and hippocampal gliosis. The modified Gallyas silver degeneration stain consistently labeled cell bodies and terminals throughout the ipsilateral cortex, axons in the gray matter-white matter interface above the corpus callosum and within the corpus callosum bilaterally, and terminals and fibers in the thalamus bilaterally. Additionally, the mouse FPI model described is immediately employable in labs already using the FPI rat model with no modifications to a pre-existing PPI apparatus.