Effects of Aquaporin-4 on edema formation following intracerebral hemorrhage
Effects of Aquaporin-4 on edema formation following intracerebral hemorrhage
复制标题
Aquaporin-4对脑出血后水肿形成的影响
DOI：
10.1016/j.expneurol.2010.01.015
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发表时间：
2010-06-01
影响因子：
5.3
通讯作者：
Dong, Qiang
中科院分区：
文献类型：
--
作者：
Tang, Yuping;Wu, Pin;Dong, Qiang
目的：脑出血 (ICH) 占所有中风的 10% 至 15%，且发病率和死亡率较高。迄今为止，人们对 AQP4（Aquaporin-4）的作用知之甚少，AQP4 在毛细血管周围星形胶质细胞足突和脑出血后水肿形成中大量表达。本研究的目的是利用AQP4(-/-)小鼠探讨AQP4在ICH后水肿形成中的作用。方法：将5μl自体全血显微注射到AQP4(+/+)和AQP4(-/-)小鼠纹状体中诱导ICH。我们比较了ICH后AQP4(+/+)和AQP4(-/-)小鼠的神经功能缺损、整个出血同侧半球的脑水肿含量、血肿周围脑组织比重、伊文思蓝渗漏和脑微血管超微结构。还用尼氏染色和TUNEL染色检测了组织学变化。结果：我们的实验显示AQP4(+/+)小鼠中ICH后AQP4表达显着增加。 AQP4缺失加重了整个出血同侧半球的神经功能缺损和脑水肿内容。此外，它还能降低血肿周围脑组织的比重。此外，它还增强了伊文思蓝渗漏和脑微血管超微结构的损伤。组织学还显示，ICH后AQP4(-/-)小鼠的尼氏染色较少，而TUNEL染色较多。结论：这些结果表明，AQP4缺失会增加ICH损伤，包括水肿形成、血脑屏障损伤和神经元死亡/TUNEL阳性细胞。进一步研究 ICH 后激活的 AQP4 表达的保护作用可能为 ICH 引起的脑损伤提供有用的治疗靶点。 (C) 2010 Elsevier Inc. 保留所有权利。
Objective: Intracerebral hemorrhage (ICH) constitutes 10% to 15% of all strokes and is associated with high morbidity and mortality. To date, little is known about the role of AQP4 (Aquaporin-4), which is abundantly expressed in pericapillary astrocyte foot processes and in edema formation after intracerebral hemorrhage. The purpose of this study was to examine the role of AQP4 in edema formation after ICH by using AQP4(-/-) mice.Methods: ICH was induced by microinjecting 5 mu l autologous whole blood into the striatum of AQP4(+/+) and AQP4(-/-) mice. We compared neurological deficits, brain edema contents of whole hemorrhagic ipsilateral hemisphere, specific gravity of brain tissue surrounding hematoma, Evans blue leakage and ultrastructure of brain microvessels between AQP4(+/+) and AQP4(-/-) mice following ICH. Histological changes were also detected with Nissl's staining and TUNEL staining.Results: Our experiments showed a significant increase of AQP4 expression following ICH in AQP4(+/+) mice. AQP4 deletion aggravated neurological deficits and brain edema contents of whole hemorrhagic ipsilateral hemisphere. Besides, it also reduced the specific gravity of brain tissue surrounding hematoma. Moreover, it enhanced Evans blue leakage and ultrastructure of brain microvessel damage. Histology also showed less Nissl's staining and more TUNEL staining in AQP4(-/-) mice following ICH.Conclusions: These results suggest that AQP4 deletion increases ICH damage, including edema formation, blood-brain barrier damage and neuronal death/TUNEL-positive cells. Further studies on the protective role of activated AQP4 expression following ICH may provide useful therapeutic target for ICH-induced brain injury. (C) 2010 Elsevier Inc. All rights reserved.