Differential aquaporin 4 expression during edema build-up and resolution phases of brain inflammation.
Differential aquaporin 4 expression during edema build-up and resolution phases of brain inflammation.
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DOI：
10.1186/1742-2094-8-143
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发表时间：
2011-10-19
影响因子：
9.3
通讯作者：
Dousset V
中科院分区：
文献类型：
--
作者：
Tourdias T;Mori N;Dragonu I;Cassagno N;Boiziau C;Aussudre J;Brochet B;Moonen C;Petry KG;Dousset V
血管源性水肿在许多与脑部炎症相关的脑部疾病中动态累积，这是患者护理中令人担心的水肿恶化的关键步骤。水通过血脑屏障（BBB）开口进入被认为在水肿形成中发挥作用。然而，人们对水肿消退的机制仍知之甚少。由于水通道水通道蛋白 4 (AQP4) 为解决血管性水肿提供了重要途径，因此我们研究了 AQP4 表达的时间过程，以更好地了解其在对抗血管性水肿恶化方面的潜在作用。通过注射溶血卵磷脂在大鼠脑中诱导局灶性炎症，并在第 1、3、7、14 和 20 天时使用体内 MRI 与用作水含量标记的表观扩散系数 (ADC) 测量相结合，以及用于量化 AQP4 表达的分子和组织学方法进行评估。还对活动性炎症标志物（巨噬细胞、BBB 通透性和白细胞介素 1β）和疤痕标志物（神经胶质增生）进行了定量。这种脑炎症动物模型展示了水肿发展的两个阶段：活动性炎症期间的初始水肿累积阶段，在 3 天后达到峰值（ADC 增加），随后是注射后持续 7 至 20 天的水肿消退阶段（ADC 减少），并伴有神经胶质疤痕形成。在形成阶段观察到 AQP4 适度上调，但在继发性水肿消退阶段观察到 AQP4 表达更强的转录和翻译水平。我们得出的结论是，AQP4 表达存在时间滞后，只有在延迟期后才实现更显着的上调。考虑到 AQP4 表达不足以抵抗积聚阶段的水流入，而第二个更明显但延迟的上调涉及消退阶段，AQP4 表达的这种变化似乎是水肿加剧的重要决定因素。在许多临床情况下观察到的水肿恶化，更好地从病理生理学角度理解，对于寻求新的治疗策略至关重要。
Vasogenic edema dynamically accumulates in many brain disorders associated with brain inflammation, with the critical step of edema exacerbation feared in patient care. Water entrance through blood-brain barrier (BBB) opening is thought to have a role in edema formation. Nevertheless, the mechanisms of edema resolution remain poorly understood. Because the water channel aquaporin 4 (AQP4) provides an important route for vasogenic edema resolution, we studied the time course of AQP4 expression to better understand its potential effect in countering the exacerbation of vasogenic edema. Focal inflammation was induced in the rat brain by a lysolecithin injection and was evaluated at 1, 3, 7, 14 and 20 days using a combination of in vivo MRI with apparent diffusion coefficient (ADC) measurements used as a marker of water content, and molecular and histological approaches for the quantification of AQP4 expression. Markers of active inflammation (macrophages, BBB permeability, and interleukin-1β) and markers of scarring (gliosis) were also quantified. This animal model of brain inflammation demonstrated two phases of edema development: an initial edema build-up phase during active inflammation that peaked after 3 days (ADC increase) was followed by an edema resolution phase that lasted from 7 to 20 days post injection (ADC decrease) and was accompanied by glial scar formation. A moderate upregulation in AQP4 was observed during the build-up phase, but a much stronger transcriptional and translational level of AQP4 expression was observed during the secondary edema resolution phase. We conclude that a time lag in AQP4 expression occurs such that the more significant upregulation was achieved only after a delay period. This change in AQP4 expression appears to act as an important determinant in the exacerbation of edema, considering that AQP4 expression is insufficient to counter the water influx during the build-up phase, while the second more pronounced but delayed upregulation is involved in the resolution phase. A better pathophysiological understanding of edema exacerbation, which is observed in many clinical situations, is crucial in pursuing new therapeutic strategies.
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影响因子：
4.2
作者：
Ribeiro, Marlise de Castro;Hirt, Lorenz;Badaut, Jerome
通讯作者：
Badaut, Jerome
影响因子：
82.9
作者：
Manley, GT;Fujimura, M;Verkman, AS
通讯作者：
Verkman, AS
影响因子：
4.8
作者：
Papadopoulos, MC;Verkman, AS
通讯作者：
Verkman, AS
影响因子：
4.8
作者：
Auguste, Kurtis I.;Jin, Songwan;Verkman, A. S.
通讯作者：
Verkman, A. S.
影响因子：
3.3
作者：
Manley, GT;Binder, DK;Verkman, AS
通讯作者：
Verkman, AS