Department of Pathology and Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA.
Biomedical Sciences Graduate Program, University of California San Francisco, San Francisco, CA, USA.
Nat Neurosci. 2024 Nov;27(11):2115-2129. doi: 10.1038/s41593-024-01769-2. Epub 2024 Sep 30.
Germinal matrix hemorrhage (GMH) is a devastating neurodevelopmental condition affecting preterm infants, but why blood vessels in this brain region are vulnerable to rupture remains unknown. Here we show that microglia in prenatal mouse and human brain interact with nascent vasculature in an age-dependent manner and that ablation of these cells in mice reduces angiogenesis in the ganglionic eminences, which correspond to the human germinal matrix. Consistent with these findings, single-cell transcriptomics and flow cytometry show that distinct subsets of CD45 cells from control preterm infants employ diverse signaling mechanisms to promote vascular network formation. In contrast, CD45 cells from infants with GMH harbor activated neutrophils and monocytes that produce proinflammatory factors, including azurocidin 1, elastase and CXCL16, to disrupt vascular integrity and cause hemorrhage in ganglionic eminences. These results underscore the brain's innate immune cells in region-specific angiogenesis and how aberrant activation of these immune cells promotes GMH in preterm infants.
脑室内出血（GMH）是一种严重影响早产儿的神经发育疾病，但为什么这个大脑区域的血管容易破裂仍然未知。在这里，我们表明，产前小鼠和人类大脑中的小胶质细胞以年龄依赖的方式与新生血管相互作用，并且在小鼠中清除这些细胞会减少神经节隆起中的血管生成，神经节隆起相当于人类的生发基质。与这些发现一致，单细胞转录组学和流式细胞术表明，来自对照早产儿的不同 CD45 细胞亚群采用多种信号机制来促进血管网络的形成。相比之下，GMH 婴儿的 CD45 细胞中含有活化的中性粒细胞和单核细胞，它们产生包括天青杀素 1、弹性蛋白酶和 CXCL16 在内的促炎因子，破坏血管完整性并导致神经节隆起出血。这些结果强调了大脑固有免疫细胞在区域特异性血管生成中的作用，以及这些免疫细胞的异常激活如何促进早产儿的 GMH。
