Departments of Neurosurgery (S.Y., T.A., S.K.), Graduate School of Medicine and Pharmaceutical Science, University of Toyama, Japan.
Pathology (S.Y., M.S.), Graduate School of Medicine and Pharmaceutical Science, University of Toyama, Japan.
Stroke. 2022 Nov;53(11):3465-3473. doi: 10.1161/STROKEAHA.122.039961. Epub 2022 Aug 30.
Moyamoya disease (MMD) is a very specific disorder in terms of spontaneous development of extracranial-to-intracranial collateral circulation through the dura mater, but the underlying mechanisms are unclear. This study aimed to investigate the role of the arachnoid membrane in this unique angiogenesis in MMD.
A piece of arachnoid membrane and 1- to 2-mL cerebrospinal fluid were simultaneously harvested during surgery from 26 patients with MMD. The specimens were also collected during surgery as the controls from 6 patients with atherosclerotic carotid artery diseases. The arachnoid membrane was subjected to immunohistochemistry and the cerebrospinal fluid was used to measure the concentration of cytokines using ELISA.
The number of cells positive for PDGFR (platelet-derived growth factor receptor) α was significantly higher in MMD than in the controls (5.4±3.1 versus 2.3±2.1 cells/field; =0.02). The results were same in PDGFRβ-positive cells (10.1±4.6 versus 4.8±2.8; P=0.01) and α-SMA (alpha-smooth muscle actin)-positive cells (8.8±3.1 versus 2.0±2.5; P<0.01). On multicolor immunofluorescence, 80.5±15.6% of cells positive for PDGFRα in MMD also expressed α-SMA, being significantly higher than 14.6±7.2% in the controls (<0.01). The density of collagen in the arachnoid membrane was significantly higher in MMD than in the controls (60.3±15.0% versus 40.1±15.3%; <0.01). In MMD, advanced disease stage was significantly associated with a larger number of α-SMA-positive cells in the arachnoid membrane (=0.04). On ELISA, the cerebrospinal fluid concentrations of bFGF (basic fibroblast growth factor), HGF (hepatocyte growth factor), and TGF (transforming growth factor)-β1 were significantly higher in MMD than in the controls.
Based on these findings, MMD may elevate the concentrations of angiogenic factors in the cerebrospinal fluid and then promote the proliferation of fibroblasts in the arachnoid membrane and their differentiation into myofibroblasts, which may, in turn, enhance the production of collagen essential for spontaneous collateral formation across the arachnoid membrane.
烟雾病（MMD）是一种非常特殊的疾病，其颅外-颅内侧支循环是通过硬脑膜自发形成的，但发病机制尚不清楚。本研究旨在探讨蛛网膜在 MMD 这种独特血管生成中的作用。
从 26 例 MMD 患者的手术中同时采集一块蛛网膜和 1-2 毫升脑脊液，从 6 例动脉粥样硬化性颈动脉疾病患者的手术中采集对照标本。对蛛网膜进行免疫组织化学染色，用 ELISA 法检测脑脊液中细胞因子的浓度。
MMD 患者蛛网膜中 PDGFR（血小板衍生生长因子受体）α 阳性细胞数明显高于对照组（5.4±3.1 与 2.3±2.1 个/视野；=0.02）。PDGFRβ 阳性细胞（10.1±4.6 与 4.8±2.8；P=0.01）和 α-SMA（alpha-smooth muscle actin）阳性细胞（8.8±3.1 与 2.0±2.5；P<0.01）也有相同的结果。在多色免疫荧光中，MMD 患者中 80.5±15.6%的 PDGFRα 阳性细胞也表达 α-SMA，明显高于对照组的 14.6±7.2%（<0.01）。MMD 患者蛛网膜胶原密度明显高于对照组（60.3±15.0% 与 40.1±15.3%；<0.01）。在 MMD 中，晚期疾病阶段与蛛网膜中更多的 α-SMA 阳性细胞显著相关（=0.04）。ELISA 结果显示，MMD 患者脑脊液中 bFGF（碱性成纤维细胞生长因子）、HGF（肝细胞生长因子）和 TGF-β1 浓度明显高于对照组。
基于这些发现，MMD 可能会增加脑脊液中血管生成因子的浓度，从而促进蛛网膜成纤维细胞的增殖及其向肌成纤维细胞的分化，进而增强穿过蛛网膜形成自发性侧支所必需的胶原的产生。
