Division of Behavioral Neuroscience, Institute of Nuclear Medicine & Allied Sciences, Delhi 110 054, India.
Division of Behavioral Neuroscience, Institute of Nuclear Medicine & Allied Sciences, Delhi 110 054, India.
Exp Neurol. 2020 Jul;329:113290. doi: 10.1016/j.expneurol.2020.113290. Epub 2020 Mar 30.
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.
在啮齿动物中建立实验性创伤性脑损伤 (TBI) 模型对于理解神经创伤的病理生理和神经行为后果是必要的。已经开发了许多模型来研究实验性 TBI。流体冲击损伤 (FPI) 是最广泛用于代表临床表型的模型。然而，FPI 的手术“假手术”（颅骨切除术）是实验性 TBI 的阻碍因素。我们假设，如果颅骨切除术导致大脑结构和功能发生实质性变化，它可能模拟轻度 FPI 引起的神经行为功能障碍。为了理解这一假设，将 C57BL/6 小鼠暴露于 1.2 大气压的侧方 FPI 下，并在 FPI 后第 7 天比较假手术（颅骨切除术）和对照组小鼠的神经元结构变化、海马神经发生、神经炎症和行为功能。我们观察到颅骨切除术和 FPI 均显著增加了同侧海马神经发生，如 DCX 和 Beta-III 微管蛋白免疫反应性所示。同样，CA1 和 CA3 区 GFAP 和 TMEM 免疫反应性的显著增加表明颅骨切除术模拟了 FPI 诱导的神经炎症。颅骨切除术与 FPI 的相加破坏性作用也在轴突和树突碎裂、肿胀和神经元死亡的银染色、Fluoro-jade 和 MAP-2 免疫反应性中得到了报道。暴露于假手术的小鼠握力明显下降。我们的结果表明，单纯的假手术颅骨切除术本身足以引起 TBI 样特征，因此轻度压力下的流体冲击与颅骨切除术的相加作用很小。考虑到该方法作为一种混合（局灶性和弥漫性）损伤模型，“净神经创伤严重程度”应与未受伤的对照组进行比较，而不是与假手术组进行比较，因为它是由于流体压力和颅骨切除术引起的累积损伤的结果。然而，为了了解神经创伤的长期后果，应单独量化手术假手术的恢复程度。
