Journal Article

Proinflammatory immune cells disrupt angiogenesis and promote germinal matrix hemorrhage in prenatal human brain

Di Marco, Barbara, Combes, Alexis J., Choi, Jennifer Ja-Yoon, Kang, Gugene, Zawadzki, Miriam E., Huang, Eric J., Diafos, Loukas N., Wedderburn-Pugh, Kaylee, Shaikh, Saba, Garcia-Verdugo, Jose Manuel, Kutys, Matthew L., Gonzalez-Granero, Susana, Jacobs, Kyle A., Birrueta, Janeth Ochoa, Lin, Pin-Yeh, Coufal, Nicole G., Mayo, Lakyn N., Glass, Christopher K., Valenzuela, Edward J., Chen, Jiapei, Xia, Wenlong, Tsui, Jessica, Oldham, Michael C., Alfonso, Julieta, Kriegstein, Arnold R., Crouch, Elizabeth E., Lehtinen, Maria K., Han, Claudia Z., Kelekar, Avani, Waller, Shamari, Fancy, Stephen P. J.

2024

Overview

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. Chen et al. show that subtypes of immune cells in prenatal human brain promote angiogenesis in the germinal matrix. Conversely, in preterm infants, proinflammatory immune cells disrupt angiogenesis and promote germinal matrix hemorrhage.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 14/19 / 14/28 / 14/32 / 38/91 / 631/378/1689/2608 / 631/378/2607 / 631/378/371 / 64/60 / 96/106 / 96/31 / Ablation / Angiogenesis / Animal Genetics and Genomics / Animals / Behavioral Sciences / Biological Techniques / Biomedical and Life Sciences / Biomedicine / Blood vessels / Brain / Brain - pathology / CAP37 protein / CD45 antigen / Cell activation / Cerebral Hemorrhage - pathology / CXCL16 protein / Elastase / Female / Flow cytometry / Hemorrhage / Humans / Immune system / Infant, Newborn / Infant, Premature / Infants / Inflammation / Leukocytes (neutrophilic) / Male / Mice / Mice, Inbred C57BL / Microglia / Microglia - metabolism / Monocytes / Neonates / Neovascularization, Pathologic - pathology / Network formation / Neurobiology / Neurosciences / Newborn babies / Premature babies / Transcriptomics