Laboratory of Neurobiology and UCV, Neurology IX Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy.
Department of Pharmacological and Biomolecular Sciences, Università di Milano, 20122 Milan, Italy.
Int J Mol Sci. 2023 Jan 8;24(2):1233. doi: 10.3390/ijms24021233.
Moyamoya arteriopathy (MMA) is a rare cerebrovascular disorder that causes recurrent ischemic and hemorrhagic strokes, leading young patients to severe neurological deficits. The pathogenesis of MMA is still unknown. The disease onset in a wide number of pediatric cases raises the question of the role of genetic factors in the disease's pathogenesis. In these patients, MMA's clinical course, or progression, is largely unclear. By performing a comprehensive molecular and cellular profile in the plasma and CSF, respectively, of MMA pediatric patients, our study is aimed at assessing the levels of circulating endothelial progenitor cells (cEPC) and the release of selected proteins at an early disease stage to clarify MMA pathogenesis and progression. We employed cytofluorimetric methods and immunoassays in pediatric MMA patients and matched control subjects by age and sex. We detected increased levels of cEPC in peripheral blood and an upregulation of angiogenic markers in CSF (i.e., angiopoietin-2 and VEGF-A). This finding is probably associated with deregulated angiogenesis, as stated by the moderate severity of collateral vessel network development (Suzuki III-IV). The absence of significant modulation of neurofilament light in CSF led us to rule out the presence of substantial neuronal injury in MMA children. Despite the limited cohort of pediatric patients, we found some peculiar cellular and molecular characteristics in their blood and CSF samples. Our findings may be confirmed by wider and perspective studies to identify predictive or prognostic circulating biomarkers and potential therapeutic targets for personalized care of MMA pediatric patients.
烟雾病（MMA）是一种罕见的脑血管疾病，可导致复发性缺血性和出血性中风，使年轻患者出现严重的神经功能缺损。MMA 的发病机制尚不清楚。大量儿科病例的发病提出了遗传因素在疾病发病机制中的作用问题。在这些患者中，MMA 的临床病程或进展在很大程度上尚不清楚。通过分别对 MMA 儿科患者的血浆和 CSF 进行全面的分子和细胞特征分析，我们的研究旨在评估循环内皮祖细胞（cEPC）的水平和在疾病早期阶段释放的选定蛋白，以阐明 MMA 的发病机制和进展。我们采用流式细胞术方法和免疫测定法，在儿科 MMA 患者和年龄及性别匹配的对照组中进行了检测。我们在周围血液中检测到 cEPC 水平升高，并在 CSF 中检测到血管生成标记物（即血管生成素-2 和 VEGF-A）的上调。这一发现可能与血管生成失调有关，因为侧支血管网络发育的严重程度为 Suzuki III-IV。CSF 中神经丝轻链的显著调节缺失使我们排除了 MMA 儿童存在大量神经元损伤的可能性。尽管儿科患者的队列有限，但我们在他们的血液和 CSF 样本中发现了一些特殊的细胞和分子特征。我们的发现可以通过更广泛和前瞻性的研究得到证实，以确定预测或预后的循环生物标志物和 MMA 儿科患者个体化治疗的潜在治疗靶点。
