TY  - JOUR
AU  - Richter, Mathis
AU  - Diesterbeck, Eva
AU  - Pylaeva, Ekaterina
AU  - Labusek, Nicole
AU  - Köster, Christian
AU  - Nagel, Dennis
AU  - Karsch, Laura
AU  - Fischer, Alexa Josephine
AU  - Sous, Marah
AU  - Jung, Marcel
AU  - Chevre, Raphael
AU  - Hagemann, Nina
AU  - Andersson, Erik Axel
AU  - Ek, C Joakim
AU  - Singh, Vikramjeet
AU  - Hermann, Dirk M
AU  - Gunzer, Matthias
AU  - Jablonska, Jadwiga
AU  - Felderhoff-Müser, Ursula
AU  - Bendix, Ivo
AU  - Soehnlein, Oliver
AU  - Herz, Josephine
TI  - Hypoxic-ischemic brain injury in neonatal mice sequentially recruits neutrophils with dichotomous phenotype and function.
JO  - Nature Communications
VL  - 16
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Springer Nature
M1  - DKFZ-2025-02270
SP  - 9696
PY  - 2025
AB  - 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.
KW  - Animals
KW  - Hypoxia-Ischemia, Brain: immunology
KW  - Hypoxia-Ischemia, Brain: pathology
KW  - Hypoxia-Ischemia, Brain: physiopathology
KW  - Neutrophils: immunology
KW  - Neutrophils: metabolism
KW  - Neutrophils: pathology
KW  - Animals, Newborn
KW  - Phenotype
KW  - Mice
KW  - Neutrophil Infiltration
KW  - Mice, Inbred C57BL
KW  - Brain: pathology
KW  - Brain: immunology
KW  - Oligodendroglia: pathology
KW  - Male
KW  - Disease Models, Animal
LB  - PUB:(DE-HGF)16
C6  - pmid:41184264
DO  - DOI:10.1038/s41467-025-65517-1
UR  - https://inrepo02.dkfz.de/record/305622
ER  -