Journal Article

DKFZ-2024-01961

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Proinflammatory immune cells disrupt angiogenesis and promote germinal matrix hemorrhage in prenatal human brain.

Chen, J. ; Crouch, E. E. ; Zawadzki, M. E. ; Jacobs, K. A. ; Mayo, L. N. ; Choi, J. J. ; Lin, P.-Y. ; Shaikh, S. ; Tsui, J. ; Gonzalez-Granero, S. ; Waller, S. ; Kelekar, A. ; Kang, G. ; Valenzuela, E. J. ; Birrueta, J. O. ; Diafos, L. N. ; Wedderburn-Pugh, K. ; Di Marco, B.DKFZ* ; Xia, W. ; Han, C. Z. ; Coufal, N. G. ; Glass, C. K. ; Fancy, S. P. J. ; Alfonso, J.DKFZ* ; Kriegstein, A. R. ; Oldham, M. C. ; Garcia-Verdugo, J. M. ; Kutys, M. L. ; Lehtinen, M. K. ; Combes, A. J. ; Huang, E. J.

2024
Nature America New York, NY

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Please use a persistent id in citations: doi:10.1038/s41593-024-01769-2

Abstract: 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.

Note: 2024 Nov;27(11):2115-2129

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Contributing Institute(s):

1. A230 Klinische Neurobiologie (A230)

Research Program(s):

1. 311 - Zellbiologie und Tumorbiologie (POF4-311) (POF4-311)

Appears in the scientific report 2024

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Nature ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 20 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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