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

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-de...

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Main Authors: Chen, Jiapei (Author) , Crouch, Elizabeth E. (Author) , Zawadzki, Miriam E. (Author) , Jacobs, Kyle A. (Author) , Mayo, Lakyn N. (Author) , Choi, Jennifer Ja-Yoon (Author) , Lin, Pin-Yeh (Author) , Shaikh, Saba (Author) , Tsui, Jessica (Author) , Gonzalez-Granero, Susana (Author) , Waller, Shamari (Author) , Kelekar, Avani (Author) , Kang, Gugene (Author) , Valenzuela, Edward J. (Author) , Birrueta, Janeth Ochoa (Author) , Diafos, Loukas N. (Author) , Wedderburn-Pugh, Kaylee (Author) , Di Marco, Barbara (Author) , Xia, Wenlong (Author) , Han, Claudia Z. (Author) , Coufal, Nicole G. (Author) , Glass, Christopher K. (Author) , Fancy, Stephen P. J. (Author) , Alfonso, Julieta (Author) , Kriegstein, Arnold R. (Author) , Oldham, Michael C. (Author) , Garcia-Verdugo, Jose Manuel (Author) , Kutys, Matthew L. (Author) , Lehtinen, Maria K. (Author) , Combes, Alexis J. (Author) , Huang, Eric J. (Author)
Format: Article (Journal)
Language:English
Published: November 2024
In: Nature neuroscience
Year: 2024, Volume: 27, Pages: 2115-2129
ISSN:1546-1726
DOI:10.1038/s41593-024-01769-2
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s41593-024-01769-2
Verlag, kostenfrei, Volltext: https://www.nature.com/articles/s41593-024-01769-2
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Author Notes:Jiapei Chen, Elizabeth E. Crouch, Miriam E. Zawadzki, Kyle A. Jacobs, Lakyn N. Mayo, Jennifer Ja-Yoon Choi, Pin-Yeh Lin, Saba Shaikh, Jessica Tsui, Susana Gonzalez-Granero, Shamari Waller, Avani Kelekar, Gugene Kang, Edward J. Valenzuela, Janeth Ochoa Birrueta, Loukas N. Diafos, Kaylee Wedderburn-Pugh, Barbara Di Marco, Wenlong Xia, Claudia Z. Han, Nicole G. Coufal, Christopher K. Glass, Stephen P. J. Fancy, Julieta Alfonso, Arnold R. Kriegstein, Michael C. Oldham, Jose Manuel Garcia-Verdugo, Matthew L. Kutys, Maria K. Lehtinen, Alexis J. Combes & Eric J. Huang
Description
Summary: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.
Item Description:Online veröffentlicht: 30. September 2024
Gesehen am 16.04.2025
Physical Description:Online Resource
ISSN:1546-1726
DOI:10.1038/s41593-024-01769-2

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