%0 Journal Article
%A Richter, Mathis
%A Diesterbeck, Eva
%A Pylaeva, Ekaterina
%A Labusek, Nicole
%A Köster, Christian
%A Nagel, Dennis
%A Karsch, Laura
%A Fischer, Alexa Josephine
%A Sous, Marah
%A Jung, Marcel
%A Chevre, Raphael
%A Hagemann, Nina
%A Andersson, Erik Axel
%A Ek, C Joakim
%A Singh, Vikramjeet
%A Hermann, Dirk M
%A Gunzer, Matthias
%A Jablonska, Jadwiga
%A Felderhoff-Müser, Ursula
%A Bendix, Ivo
%A Soehnlein, Oliver
%A Herz, Josephine
%T Hypoxic-ischemic brain injury in neonatal mice sequentially recruits neutrophils with dichotomous phenotype and function.
%J Nature Communications
%V 16
%N 1
%@ 2041-1723
%C [London]
%I Springer Nature
%M DKFZ-2025-02270
%P 9696
%D 2025
%X 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.
%K Animals
%K Hypoxia-Ischemia, Brain: immunology
%K Hypoxia-Ischemia, Brain: pathology
%K Hypoxia-Ischemia, Brain: physiopathology
%K Neutrophils: immunology
%K Neutrophils: metabolism
%K Neutrophils: pathology
%K Animals, Newborn
%K Phenotype
%K Mice
%K Neutrophil Infiltration
%K Mice, Inbred C57BL
%K Brain: pathology
%K Brain: immunology
%K Oligodendroglia: pathology
%K Male
%K Disease Models, Animal
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:41184264
%R 10.1038/s41467-025-65517-1
%U https://inrepo02.dkfz.de/record/305622