VASCULAR ENDOTHELIUM-DERIVED FACTORS IN STURGE-WEBER SYNDROME HYPERMYELINATION

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 最近的磁共振成像(MRI)研究表明，脑白质异常是斯特奇-韦伯综合征(SWS)的早期特征，并与认知能力下降密切相关。这些白质改变与髓鞘凝固化有关。因此，确定SWS患者超髓鞘形成的机制可能是找到延缓或抑制受影响患者认知能力下降和其他可能的皮质异常的方法的重要一步。 我们的假设是，SWS中的胶质星形细胞，无论是自身还是对软脑膜血管瘤血管内皮细胞的信号做出反应，都会产生高水平的血管内皮生长因子(或相关因子)，从而导致OPC加速增殖和随后的高髓鞘形成。我们将使用患者来源的原代细胞和少突胶质细胞前体细胞的小鼠细胞培养模型的组合来验证这一假设。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Recent magnetic resonance imaging (MRI) studies have indicated that white matter abnormalities are an early hallmark of Sturge-Weber Syndrome (SWS) and are strongly correlated with cognitive decline. These white matter changes have been linked to acclerated myelination. Identifying the mechanisms underlying hypermyelination in SWS could therefore be a significant step towards finding ways to delay or inhibit cognitive decline and possibly other cortical abnormalities in affected patients. Our hypothesis is that gliotic astrocytes in SWS, either by themselves or in response to signals from vascular endothelial cells of leptomeningial angiomas, produce elevated VEGF (or related factors) that causes accelerated OPC proliferation and subsequent hypermyelination. We will test this hypothesis using a combination of patient-derived primary cells and murine cell culture models of oligodendrocyte progenitors.