Mao Xiaoyan, Enno Terry L, Del Bigio Marc R
Department of Pathology, University of Manitoba, 715 McDermot Ave, Winnipeg MB, R3E 3P5 Canada.
Eur J Neurosci. 2006 Jun;23(11):2929-36. doi: 10.1111/j.1460-9568.2006.04829.x.
Hydrocephalus is characterized by impaired cerebrospinal fluid (CSF) flow with enlargement of the ventricular cavities of the brain and progressive damage to surrounding tissue. Bulk water movement is altered in these brains. We hypothesized that increased expression of aquaporins, which are water-permeable channel proteins, would occur in these brains to facilitate water shifts. We used quantitative (real-time) RT-PCR, Western blotting and immunohistochemistry to evaluate the brain expression of aquaporins (AQP) 1, 4, and 9 mRNA and protein in Sprague-Dawley rats rendered hydrocephalic by injection of kaolin into cistern magna. AQP4 mRNA was significantly up-regulated in parietal cerebrum and hippocampus 4 weeks and 9 months after induction of hydrocephalus (P < 0.05). Although Western blot analysis showed no significant change, there was more intense perivascular AQP4 immunoreactivity in cerebrum of hydrocephalic brains at 3-4 weeks after induction. We did not detect mRNA or protein changes in AQP1 (located in choroid plexus) or AQP9 (located in select neuron populations). Kir4.1, a potassium channel protein linked to water flux, exhibited enhanced immunoreactivity in the cerebral cortex of hydrocephalic rats; the perineuronal distribution was entirely different from that of AQP4. These results suggest that brain AQP4 up-regulation might be a compensatory response to maintain water homeostasis in hydrocephalus.
脑积水的特征是脑脊液（CSF）流动受损，伴有脑室腔扩大以及对周围组织的进行性损害。在这些大脑中，大量水分的移动发生了改变。我们推测，水通道蛋白（水通透通道蛋白）表达增加会出现在这些大脑中以促进水分转移。我们使用定量（实时）逆转录聚合酶链反应、蛋白质印迹法和免疫组织化学来评估水通道蛋白（AQP）1、4和9的mRNA和蛋白质在通过向大鼠小脑延髓池注射高岭土而导致脑积水的Sprague-Dawley大鼠大脑中的表达。在诱导脑积水后4周和9个月，顶叶大脑和海马中的AQP4 mRNA显著上调（P < 0.05）。虽然蛋白质印迹分析显示无显著变化，但在诱导后3 - 4周，脑积水大鼠大脑中血管周围的AQP4免疫反应性更强。我们未检测到位于脉络丛的AQP1或位于特定神经元群体的AQP9的mRNA或蛋白质变化。Kir4.1，一种与水通量相关的钾通道蛋白，在脑积水大鼠的大脑皮质中免疫反应性增强；其神经元周围分布与AQP4完全不同。这些结果表明，大脑AQP4上调可能是在脑积水中维持水平衡的一种代偿反应。
