Academic Neurosurgery Unit, St George's, University of London, London, UK.
Neuroscience. 2010 Apr 28;167(1):60-7. doi: 10.1016/j.neuroscience.2010.01.053. Epub 2010 Feb 1.
We investigated the role of the glial water channel protein aquaporin-4 in brain edema in a mouse model of subarachnoid hemorrhage in which 30 microl of blood was injected into the basal cisterns. Brain water content, intracranial pressure and neurological score were compared in wildtype and aquaporin-4 null mice. We also measured blood-brain barrier permeability, and the osmotic permeability of the glia limitans, one of the routes of edema elimination. Wildtype and aquaporin-4 null mice had comparable baseline brain water content, intracranial pressure and neurological score. At 6 h after blood injection, aquaporin-4 null mice developed more brain swelling than wildtype mice. Brain water content increased by 1.5+/-0.1% vs. 0.5+/-0.2% (Mean+/-Standard Error, P<0.0005) and intracranial pressure by 36+/-5 vs. 21+/-3 mm Hg (P<0.05) above pre-injection baseline, and neurological score was worse at 18.0 vs. 24.5 (median, P<0.05), respectively. Although subarachnoid hemorrhage produced comparable increases in blood-brain barrier permeability in wildtype and aquaporin-4 null mice, aquaporin-4 null mice had a twofold reduction in glia limitans osmotic permeability. We conclude that aquaporin-4 null mice manifest increased brain edema following subarachnoid hemorrhage as a consequence of reduced elimination of excess brain water.
我们在蛛网膜下腔出血模型中研究了神经胶质水通道蛋白水通道蛋白-4 在脑水肿中的作用，在该模型中向基底池内注射了 30 微升血液。在野生型和水通道蛋白-4 敲除小鼠中比较了脑水含量、颅内压和神经评分。我们还测量了血脑屏障通透性和胶质界膜的渗透，胶质界膜是水肿消除的途径之一。野生型和水通道蛋白-4 敲除小鼠的基线脑水含量、颅内压和神经评分相当。在血液注射后 6 小时，水通道蛋白-4 敲除小鼠比野生型小鼠发生更严重的脑水肿。脑水含量增加了 1.5+/-0.1%比 0.5+/-0.2%（平均值+/-标准误差，P<0.0005），颅内压增加了 36+/-5 比 21+/-3mmHg（P<0.05），神经评分分别为 18.0 比 24.5（中位数，P<0.05）更差。尽管蛛网膜下腔出血在野生型和水通道蛋白-4 敲除小鼠中引起了相似的血脑屏障通透性增加，但水通道蛋白-4 敲除小鼠的胶质界膜渗透减少了两倍。我们的结论是，水通道蛋白-4 敲除小鼠在蛛网膜下腔出血后表现出更严重的脑水肿，这是由于过多脑水的清除减少所致。
