Department of Neurological Surgery, Aichi Medical University, Nagakute, Aichi-gun, Japan.
J Neurotrauma. 2011 Jun;28(6):1127-31. doi: 10.1089/neu.2010.1498. Epub 2011 May 5.
Chronic subdural hematoma (CSDH) is an angiogenic disease that is recognized as a cause of treatable dementia with unknown pathogenesis. Vascular endothelial growth factor (VEGF), a potent growth factor regulating angiogenesis through the phosphatidylinositol 3-kinase (PI3-kinase)/Akt pathway, has been implicated in its etiology. The status of this signaling pathway in CSDH outer membranes was examined in the present study, using outer membranes obtained during trepanation surgery. Expressions of PI3-kinase, PKB-kinase, Akt, phosphorylated Akt at Ser(473) (p-Akt), endothelial nitric oxide synthase (eNOS), vascular endothelial-cadherin (VE-cadherin), and actin were examined by Western blot analysis, together with their immunohistochemistry. PI3-kinase, Akt, eNOS, and VE-cadherin were detected in all cases. The magnitude of the expression of p-Akt varied among cases; however, the localization was revealed to be present in endothelial cells of vessels in CSDH outer membranes, together with VEGF and VE-cadherin detected in endothelial cells of vessels. These findings suggest that the PI3-kinase/Akt signaling is activated in CSDH outer membranes, and indicate the possibility that the PI3 kinase/Akt pathway might be activated by VEGF and play a critical role in the angiogenesis of CSDH.
慢性硬脑膜下血肿（CSDH）是一种血管生成性疾病，被认为是一种可治疗性痴呆的病因，但发病机制尚不清楚。血管内皮生长因子（VEGF）是一种通过磷脂酰肌醇 3-激酶（PI3-kinase）/Akt 途径调节血管生成的有效生长因子，其在发病机制中具有重要作用。本研究通过钻孔手术获得的硬脑膜外膜，检测了该信号通路在 CSDH 外膜中的状态。通过 Western blot 分析和免疫组织化学检测了外膜中 PI3-激酶、PKB-激酶、Akt、磷酸化 Akt 丝氨酸 473 位（p-Akt）、内皮型一氧化氮合酶（eNOS）、血管内皮钙黏蛋白（VE-cadherin）和肌动蛋白的表达。所有病例均检测到 PI3-激酶、Akt、eNOS 和 VE-cadherin。p-Akt 的表达量因病例而异，但定位显示存在于 CSDH 外膜血管内皮细胞中，与血管内皮细胞中的 VEGF 和 VE-cadherin 一起存在。这些发现表明，PI3-kinase/Akt 信号在 CSDH 外膜中被激活，并提示 PI3 激酶/Akt 途径可能被 VEGF 激活，并在 CSDH 的血管生成中发挥关键作用。
