Department of Neurosurgery, University of Maryland School of Medicine, 10 S. Pine St., MSTF 634, Baltimore, MD, 21201-1595, USA.
Departments of Pathology, University of Maryland School of Medicine, 10 S. Pine St., MSTF 634, Baltimore, MD, 21201-1595, USA.
Acta Neuropathol Commun. 2015 Sep 30;3:61. doi: 10.1186/s40478-015-0239-6.
Ischemic stroke, a major cause of mortality, is frequently accompanied by life-threatening cerebral edema. Aquaporin-4 (Aqp4), an astrocytic transmembrane water channel, is an important molecular contributor to cerebral edema formation. Past studies of Aqp4 expression and localization after ischemia examined grey matter exclusively. However, as white matter astrocytes differ developmentally, physiologically, and molecularly from grey matter astrocytes, we hypothesized that functionally important regional heterogeneity exists in Aqp4 expression and subcellular localization following cerebral ischemia.
Subcellular localization of Aqp4 was compared between cortical and white matter astrocytes in postmortem specimens of patients with focal ischemic stroke versus controls. Subcellular localization and expression of Aqp4 was examined in rats subjected to experimental stroke. Volumetric analysis was performed on the cortex and white matter of rats subjected to experimental stroke. Following cerebral ischemia, cortical astrocytes exhibited reduced perivascular Aqp4 and unchanged Aqp4 protein abundance. In contrast, white matter astrocytes exhibited increased perivascular and plasmalemmal Aqp4 and a 2.2- to 6.2-fold increase in Aqp4 isoform abundance. Ischemic white matter swelled by approximately 40 %, while cortex swelled by approximately 9 %.
The findings reported here raise the possibility that cerebral white matter may play a heretofore underappreciated role in the formation of cerebral edema following ischemia.
缺血性中风是一种主要的致死原因，常伴有危及生命的脑水肿。水通道蛋白 4（AQP4）是一种星形细胞跨膜水通道，是脑水肿形成的重要分子贡献者。过去对缺血后 AQP4 表达和定位的研究仅检查了灰质。然而，由于白质星形细胞在发育、生理和分子水平上与灰质星形细胞不同，我们假设在脑缺血后 AQP4 的表达和亚细胞定位存在功能上重要的区域异质性。
在局灶性缺血性中风患者与对照组的尸检标本中比较了皮质和白质星形细胞中 AQP4 的亚细胞定位。在实验性中风大鼠中检查了 AQP4 的亚细胞定位和表达。对实验性中风大鼠的皮质和白质进行了体积分析。在脑缺血后，皮质星形细胞表现出血管周围 AQP4 的减少和 AQP4 蛋白丰度不变。相比之下，白质星形细胞表现出血管周围和质膜 AQP4 的增加，以及 AQP4 同工型丰度增加 2.2-6.2 倍。缺血性白质肿胀约 40%，而皮质肿胀约 9%。
这里报告的发现提出了一种可能性，即脑白质可能在缺血后脑水肿形成中发挥了迄今为止被低估的作用。
