Background Traumatic brain edema (TBE) is caused by a specific water channel mediated by membrane aquaporins. Aquaporin-4 (AQP4) plays an especially important role in this process, but the relationship between AQP4 and TBE remains unclear. The purpose of this study was to explore expression of AQP4 in the hippocampus after traumatic brain injury (TBI), as well as the effect of brain edema on skeletal protein and its function in hippocampal neurons. Methods The adult male Wistar rats we divided into a sham group and a TBI group, the latter of which was further divided into 1, 3, 6, 12, 24 and 72 hours (h) and 15 days (d) post injury subgroups. A proper TBI model was established, and brain edema was assessed in each group by water content. We measured the abundance of various proteins, including hypoxia inducible factor-1α (HIF-1α), AQP4, microtubule-associated protein 2 (MAP2), tau-5 protein, phosphorylated level of TAU, synaptophysin, cyclic adenosine monophosphate response element binding protein (CREB), phosphorylated CREB and general control nonrepressed 2, in each group. Hippocampal neurons and spatial memory test were analyzed in different time points. Results Compared with that in the sham group, the level of AQP4 in hippocampal neurons began to significantly increase at 1 h post TBI and then decreased at 15 d post TBI. During this time frame, AQP4 level peaked at 12 and 72 h, and these peaks were closely correlated with high brain water content. HIF-1α displayed a similar trend. Conversely, levels of MAP2 began to decrease at 1 h post TBI and then increase at 15 d post TBI. In addition, the most severe brain edema in rats was found at 24 h post TBI, with neuronal loss and hippocampal dendritic spine injury. Compared to those in the sham group, rats in the TBI groups had significantly prolonged latency and significantly shortened exploration time. Conclusions AQP4 level was closely correlated with severity of brain edema, and abnormal levels thereof aggravated such severity after TBI.

中文翻译：

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Aquaporin-4 通过加重脑水肿的严重程度成为创伤性脑损伤的潜在药物靶点

背景创伤性脑水肿 (TBE) 是由膜水通道蛋白介导的特定水通道引起的。Aquaporin-4 (AQP4) 在这一过程中发挥着特别重要的作用，但 AQP4 与 TBE 之间的关系仍不清楚。本研究旨在探讨创伤性脑损伤（TBI）后海马AQP4的表达，以及脑水肿对骨骼蛋白及其在海马神经元中的作用的影响。方法将成年雄性Wistar大鼠分为假手术组和TBI组，TBI组又分为伤后1、3、6、12、24、72小时（h）和15天（d）亚组。建立适当的TBI模型，并通过含水量评估各组的脑水肿。我们测量了各种蛋白质的丰度，包括缺氧诱导因子 1α (HIF-1α)、AQP4、每组微管相关蛋白 2 (MAP2)、tau-5 蛋白、TAU 磷酸化水平、突触素、环磷酸腺苷反应元件结合蛋白 (CREB)、磷酸化 CREB ​​和一般对照非抑制 2。在不同时间点分析海马神经元和空间记忆测试。结果与假手术组相比，海马神经元AQP4水平在TBI后1 h开始显着升高，在TBI后15 d下降。在此期间，AQP4 水平在 12 小时和 72 小时达到峰值，这些峰值与高脑含水量密切相关。HIF-1α 表现出类似的趋势。相反，MAP2 水平在 TBI 后 1 小时开始下降，然后在 TBI 后 15 天增加。此外，大鼠脑水肿最严重的是在 TBI 后 24 小时，伴有神经元丢失和海马树突棘损伤。与假手术组相比，TBI组大鼠潜伏期显着延长，探查时间显着缩短。结论 AQP4水平与脑水肿的严重程度密切相关，其异常水平会加重TBI后脑水肿的严重程度。