VASCULAR ENDOTHELIUM-DERIVED FACTORS IN STURGE-WEBER SYNDROME HYPERMYELINATION

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 最近的磁共振成像（MRI）研究表明，白色物质异常是Sturge-Weber综合征（SWS）的早期标志，并与认知能力下降密切相关。 这些白色物质的变化与髓鞘形成的加速有关。 因此，确定SWS中髓鞘过度形成的潜在机制可能是寻找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，胶质星形胶质细胞在SWS，无论是通过自己或在响应信号从血管内皮细胞的软脑膜血管瘤，产生升高的VEGF（或相关因素），导致加速OPC增殖和随后的髓鞘形成。 我们将使用患者来源的原代细胞和少突胶质细胞祖细胞的鼠细胞培养模型的组合来检验这一假设。

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.