Yao Xiaoming, Derugin Nikita, Manley Geoffrey T, Verkman A S
Department of Neurological Surgery, University of California, San Francisco, CA 94143, USA; Brain and Spinal Injury Center, University of California, San Francisco, CA 94143, USA; Departments of Medicine and Physiology, University of California, San Francisco, CA 94143, USA.
Department of Neurological Surgery, University of California, San Francisco, CA 94143, USA; Brain and Spinal Injury Center, University of California, San Francisco, CA 94143, USA.
Neurosci Lett. 2015 Jan 1;584:368-72. doi: 10.1016/j.neulet.2014.10.040. Epub 2014 Nov 1.
Aquaporin-4 (AQP4) is a water channel expressed in astrocyte end-feet lining the blood-brain barrier. AQP4 deletion in mice is associated with improved outcomes in global cerebral ischemia produced by transient carotid artery occlusion, and focal cerebral ischemia produced by permanent middle cerebral artery occlusion (MCAO). Here, we investigated the consequences of 1-h transient MCAO produced by intraluminal suture blockade followed by 23 h of reperfusion. In nine AQP4(+/+) and nine AQP4(-/-) mice, infarct volume was significantly reduced by an average of 39 ± 4% at 24h in AQP4(-/-) mice, cerebral hemispheric edema was reduced by 23 ± 3%, and Evans Blue extravasation was reduced by 31 ± 2% (mean ± SEM). Diffusion-weighted magnetic resonance imaging showed greatest reduction in apparent diffusion coefficient around the occlusion site after reperfusion, with remarkably lesser reduction in AQP4(-/-) mice. The reduced infarct volume in AQP4(-/-) mice following transient MCAO supports the potential utility of therapeutic AQP4 inhibition in stroke.
水通道蛋白4（AQP4）是一种在血脑屏障周围的星形胶质细胞终足中表达的水通道。小鼠体内AQP4缺失与短暂性颈动脉闭塞所致全脑缺血以及永久性大脑中动脉闭塞（MCAO）所致局灶性脑缺血的改善结局相关。在此，我们研究了通过腔内缝线阻塞造成1小时短暂性MCAO并随后再灌注23小时的后果。在9只AQP4(+/+)小鼠和9只AQP4(-/-)小鼠中，AQP4(-/-)小鼠在24小时时梗死体积平均显著减小39±4%，脑半球水肿减轻23±3%，伊文思蓝外渗减少31±2%（平均值±标准误）。扩散加权磁共振成像显示再灌注后闭塞部位周围表观扩散系数降低幅度最大，而AQP4(-/-)小鼠的降低幅度明显较小。短暂性MCAO后AQP4(-/-)小鼠梗死体积减小支持了治疗性抑制AQP4在中风治疗中的潜在效用。
