Modeling experimental traumatic brain injury (TBI) in rodents is necessarily required to understand the pathophysiological and neurobehavioral consequences of neurotrauma. Numerous models have been developed to study experimental TBI. Fluid percussion injury (FPI) is the most extensively used model to represent clinical phenotypes. Nevertheless, the surgical 'sham' procedure (craniectomy), a prerequisite of FPI, is the impeding factor in experimental TBI. We hypothesized that if craniectomy causes substantial structural and functional changes in the brain, it might mimic the mild FPI-induced neurobehavioral dysfunctions. To understand the hypothesis, C57BL/6 mice were exposed to lateral FPI at 1.2 atm pressure and changes in the neuronal architecture, hippocampal neurogenesis, neuroinflammation, and behavioral functions were compared to the sham (craniectomy) and control mice at day 7 post-FPI. We observed that both the craniectomy and FPI significantly augmented the ipsilateral hippocampal neurogenesis as evaluated by DCX and Beta-III tubulin immunoreactivity. Similarly, a significant increase in GFAP and TMEM immunoreactivity in CA1 and CA3 regions showed that craniectomy mimics FPI-induced neuroinflammation. The additive damaging effect of craniectomy with FPI was also reported in the term of axonal and dendritic fragmentation, swelling and neuronal death using silver staining, Fluoro-jade, and MAP-2 immunoreactivity. Sham-exposed mice showed a significant functional decrease in grip strength. Our results indicate that sham craniectomy itself is enough to cause TBI like characteristics, and thus fluid percussion at mild pressure is minimally additive with craniectomy. Considering the method as a mixed (focal & diffused) injury model, the 'net neurotrauma severity' should be compared with naïve control instead of the sham as it is an outcome of cumulative damage due to fluid pressure and craniectomy. Nevertheless, to understand the long term consequences of neurotrauma, the extent of recovery in surgical sham may separately be quantified.

中文翻译：

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低压液体撞击声对假性颅骨切除术引起的神经行为改变的影响最小：对实验性脑外伤模型的意义。

为了解啮齿动物的病理生理和神经行为后果，必须对啮齿动物的实验性颅脑损伤（TBI）进行建模。已经开发了许多模型来研究实验性TBI。液压冲击损伤（FPI）是最广泛使用的代表临床表型的模型。尽管如此，外科“假”手术（颅骨切除术）是FPI的先决条件，是实验性TBI的障碍因素。我们假设，如果颅骨切除术引起大脑实质性的结构和功能改变，则可能模仿轻度FPI引起的神经行为功能障碍。为了解这一假设，将C57BL / 6小鼠在1.2 atm的压力下暴露于侧向FPI，并改变神经元结构，海马神经发生，神经炎症，FPI后第7天，将假肢和行为功能与假手术（颅骨切除术）和对照组进行比较。我们观察到，通过DCX和Beta-III微管蛋白免疫反应性评估，颅骨切除术和FPI均显着增强了同侧海马神经发生。同样，CA1和CA3区的GFAP和TMEM免疫反应性显着增加，表明颅骨切除术模仿了FPI诱导的神经炎症。还报道了使用FPI进行的颅骨切除术的附加损害作用，其中包括使用银染，荧光玉石和MAP-2免疫反应性的轴突和树突破碎，肿胀和神经元死亡。假接触的小鼠表现出明显的抓地力功能下降。我们的结果表明，深部颅骨切除术本身足以引起类似TBI的特征，因此，在颅骨切除术中，在轻度压力下的液体撞击声几乎不会增加。考虑到该方法是混合的（局灶性和弥散性）损伤模型，应将“净神经创伤严重程度”与单纯对照而非假手术进行比较，因为它是由于液压和颅骨切除术造成的累积损伤的结果。但是，要了解神经外伤的长期后果，可以单独量化手术假手术的恢复程度。