Skjolding Anders D, Rowland Ian J, Søgaard Lise V, Praetorius Jeppe, Penkowa Milena, Juhler Marianne
University Clinic of Neurosurgery, Rigshospitalet, Copenhagen, Denmark.
Cerebrospinal Fluid Res. 2010 Nov 5;7:20. doi: 10.1186/1743-8454-7-20.
The water channel protein aquaporin-4 (AQP4) is reported to be of possible major importance for accessory cerebrospinal fluid (CSF) circulation pathways. We hypothesized that changes in AQP4 expression in specific brain regions correspond to the severity and duration of hydrocephalus.
Hydrocephalus was induced in adult rats (~8 weeks) by intracisternal kaolin injection and evaluated after two days, one week and two weeks. Using magnetic resonance imaging (MRI) we quantified lateral ventricular volume, water diffusion and blood-brain barrier properties in hydrocephalic and control animals. The brains were analysed for AQP4 density by western blotting and localisation by immunohistochemistry. Double fluorescence labelling was used to study cell specific origin of AQP4.
Lateral ventricular volume was significantly increased over control at all time points after induction and the periventricular apparent diffusion coefficient (ADC) value significantly increased after one and two weeks of hydrocephalus. Relative AQP4 density was significantly decreased in both cortex and periventricular region after two days and normalized after one week. After two weeks, periventricular AQP4 expression was significantly increased. Relative periventricular AQP4 density was significantly correlated to lateral ventricular volume. AQP4 immunohistochemical analysis demonstrated the morphological expression pattern of AQP4 in hydrocephalus in astrocytes and ventricular ependyma. AQP4 co-localized with astrocytic glial fibrillary acidic protein (GFAP) in glia limitans. In vascular structures, AQP4 co-localized to astroglia but not to microglia or endothelial cells.
AQP4 levels are significantly altered in a time and region dependent manner in kaolin-induced hydrocephalus. The presented data suggest that AQP4 could play an important neurodefensive role, and may be a promising future pharmaceutical target in hydrocephalus and CSF disorders.
据报道，水通道蛋白4（AQP4）对脑脊液（CSF）的辅助循环途径可能具有重要意义。我们推测特定脑区AQP4表达的变化与脑积水的严重程度和持续时间相对应。
通过脑池内注射高岭土在成年大鼠（约8周龄）中诱导脑积水，并在两天、一周和两周后进行评估。使用磁共振成像（MRI）对脑积水大鼠和对照动物的侧脑室体积、水扩散和血脑屏障特性进行量化。通过蛋白质免疫印迹分析脑内AQP4密度，并通过免疫组织化学进行定位。使用双重荧光标记研究AQP4的细胞特异性来源。
诱导后所有时间点的侧脑室体积均显著高于对照组，脑积水1周和2周后侧脑室周围表观扩散系数（ADC）值显著增加。两天后皮质和脑室周围区域的相对AQP4密度显著降低，一周后恢复正常。两周后，脑室周围AQP4表达显著增加。脑室周围相对AQP4密度与侧脑室体积显著相关。AQP4免疫组织化学分析显示了脑积水时星形胶质细胞和室管膜中AQP4的形态学表达模式。在胶质界膜中，AQP4与星形胶质细胞的胶质纤维酸性蛋白（GFAP）共定位。在血管结构中，AQP4与星形胶质细胞共定位，但与小胶质细胞或内皮细胞不共定位。
在高岭土诱导的脑积水中，AQP4水平以时间和区域依赖性方式显著改变。所呈现的数据表明，AQP4可能发挥重要的神经保护作用，并且可能是未来脑积水和脑脊液疾病中有前景的药物靶点。
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