Department of Physiology and Biophysics, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA.
FASEB J. 2022 Jun;36(6):e22339. doi: 10.1096/fj.202200120R.
Germinal matrix-intraventricular hemorrhage (GM-IVH) is the most devastating neurological complication in premature infants. GM-IVH usually begins in the GM, a highly vascularized region of the developing brain where glial and neuronal precursors reside underneath the lateral ventricular ependyma. Previous studies using human fetal tissue have suggested increased angiogenesis and paucity of pericytes as key factors contributing to GM-IVH pathogenesis. Yet, despite its relevance, the mechanisms underlying the GM vasculature's susceptibility to hemorrhage remain poorly understood. To gain better understanding on the vascular dynamics of the GM, we performed a comprehensive analysis of the mouse GM vascular endothelium and pericytes during development. We hypothesize that vascular development of the mouse GM will provide a good model for studies of human GM vascularization and provide insights into the role of pericytes in GM-IVH pathogenesis. Our findings show that the mouse GM presents significantly greater vascular area and vascular branching compared to the developing cortex (CTX). Analysis of pericyte coverage showed abundance in PDGFRβ-positive and NG2-positive pericyte coverage in the GM similar to the developing CTX. However, we found a paucity in Desmin-positive pericyte coverage of the GM vasculature. Our results underscore the highly angiogenic nature of the GM and reveal that pericytes in the developing mouse GM exhibit distinct phenotypical and likely functional characteristics compared to other brain regions which might contribute to the high susceptibility of the GM vasculature to hemorrhage.
脑室内出血(IVH)是早产儿最严重的神经并发症。IVH 通常始于生发基质(GM),GM 是大脑发育过程中血管化程度极高的区域,其中神经胶质和神经元前体位于侧脑室室管膜下。先前使用人胎儿组织的研究表明,血管生成增加和周细胞减少是导致 GM-IVH 发病机制的关键因素。然而,尽管其相关性很高,但 GM 血管对出血的易感性的机制仍知之甚少。为了更好地了解 GM 的血管动力学,我们对发育过程中鼠标 GM 的血管内皮细胞和周细胞进行了全面分析。我们假设,鼠标 GM 的血管发育将为研究人类 GM 血管生成提供一个很好的模型,并深入了解周细胞在 GM-IVH 发病机制中的作用。我们的研究结果表明,与发育中的皮质(CTX)相比,鼠标 GM 表现出明显更大的血管面积和血管分支。周细胞覆盖分析表明,GM 中 PDGFRβ阳性和 NG2 阳性周细胞的覆盖丰富,与发育中的 CTX 相似。然而,我们发现 GM 血管中的 Desmin 阳性周细胞覆盖不足。我们的研究结果强调了 GM 的高度血管生成特性,并揭示了发育中的鼠标 GM 中的周细胞表现出独特的表型和可能的功能特征,这可能导致 GM 血管对出血的高度易感性。