Hypoxic-ischemic brain injury in neonatal mice sequentially recruits neutrophils with dichotomous phenotype and function

Mathis Richter, Eva Diesterbeck, Ekaterina Pylaeva, Nicole Labusek, Christian Köster, Dennis Nagel, Laura Karsch, Alexa Josephine Fischer, Marah Sous, Marcel Jung, Raphael Chevre, Nina Hagemann, Erik Axel Andersson, C. Joakim Ek, Vikramjeet Singh, Dirk M. Hermann, Matthias Gunzer, Jadwiga Jablonska, Ursula Felderhoff-Müser, Ivo Bendix, Oliver Soehnlein and Josephine Herz ()
Additional contact information
Mathis Richter: University Duisburg-Essen
Eva Diesterbeck: University Duisburg-Essen
Ekaterina Pylaeva: University Duisburg-Essen
Nicole Labusek: University Duisburg-Essen
Christian Köster: University Duisburg-Essen
Dennis Nagel: University Duisburg-Essen
Laura Karsch: University Duisburg-Essen
Alexa Josephine Fischer: University Duisburg-Essen
Marah Sous: University Duisburg-Essen
Marcel Jung: University Duisburg-Essen
Raphael Chevre: University of Münster
Nina Hagemann: University Duisburg-Essen
Erik Axel Andersson: University of Gothenburg
C. Joakim Ek: University of Gothenburg
Vikramjeet Singh: University Duisburg-Essen
Dirk M. Hermann: University Duisburg-Essen
Matthias Gunzer: University Duisburg-Essen
Jadwiga Jablonska: University Duisburg-Essen
Ursula Felderhoff-Müser: University Duisburg-Essen
Ivo Bendix: University Duisburg-Essen
Oliver Soehnlein: University of Münster
Josephine Herz: University Duisburg-Essen

Nature Communications, 2025, vol. 16, issue 1, 1-19

Abstract: Abstract Neonatal encephalopathy caused by hypoxia-ischemia (HI) leads to a strong neutrophil infiltration. The long-held assumption that neutrophils act exclusively as tissue-damaging cells, is challenged by increasing evidence of a profound neutrophil heterogeneity. Here, we uncovered a pronounced phenotypical and functional diversification of neutrophils in neonatal mice depending on the disease stage. Neutrophil infiltration was biphasic, peaking 1 and 7 days after HI. Early brain-infiltrating neutrophils displayed a hyperactivated phenotype, whereas neutrophils at day 7 exhibited an angiogenic phenotype with high Siglec-F expression. Acute neutrophil depletion protected against neural cell death, associated with decreased hyperactivity in adolescent animals. Delayed neutrophil depletion impaired vascular and oligodendrocyte regeneration, resulting in exacerbated alterations of anxiety-related behavior and myelination deficits. These findings suggest a divergent function of neutrophils, with early neutrophils aggravating tissue damage and late neutrophils contributing to neurological recovery. The disease stage-dependent neutrophil diversification offers new possibilities to identify disease-stage-specific therapeutic targets.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-65517-1 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-65517-1

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-65517-1

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().