Neutrophil heterogeneity and crosstalk with cerebral-resident cells: therapeutic targets for ischemic stroke
4 affiliations
- 1Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- 2Department of Neurology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei China
- 3State Key Laboratory of Advanced Refractories, Wuhan University of Science and Technology, Wuhan, China
- 4Department of Pharmacy, Zhongnan Hospital of Wuhan University, Wuhan, Hubei China
Abstract
Acute ischemic stroke elicits a robust inflammatory response within the brain. As one of the first peripheral immune cells to infiltrate the ischemic parenchyma, neutrophils show high heterogeneity and engage in complex crosstalk with resident brain cells. In this review, we first delineate the temporal dynamics of neutrophil mobilization after ischemic stroke, emphasizing their early and sustained accumulation in the ischemic brain. We then highlight recent advances in understanding neutrophil heterogeneity following ischemic stroke, with a particular focus on the skull–brain axis revealed by single-cell RNA sequencing. Additionally, we discuss the multifaceted interactions between neutrophils and parenchymal cells, including endothelial cells, neurons, microglia, and astrocytes after ischemic stroke. Finally, we expand the translational perspective by discussing emerging therapeutic approaches targeting neutrophils, NETosis, or specific neutrophil subsets in ischemic stroke. Unlike prior reviews that broadly focused on inflammatory networks, the present review specifically emphasizes the crosstalk between distinct neutrophil subsets and cerebral-resident cells, and integrates the latest single-cell RNA sequencing discoveries, including the newly identified skull–brain axis and a critical discussion of dichotomous models. Collectively, a comprehensive understanding of this intricate cellular network may help elucidate neutrophil heterogeneity, and future therapeutic strategies should shift from broad neutrophil depletion to precise targeting of pathogenic subsets to preserve potential repair functions.
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BibTeX
@article{yu2026neutrophil,
title = {{Neutrophil heterogeneity and crosstalk with cerebral-resident cells: therapeutic targets for ischemic stroke}},
author = {Yulin Yu and Ying Bi and Hao Song and Dong Sun and Siyu Huang and Jianhua Wu and Bin Mei and Zhifang Li},
journal = {Journal of Translational Medicine},
year = {2026},
month = aug,
doi = {10.1186/s12967-026-08786-8},
url = {https://doi.org/10.1186/s12967-026-08786-8},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Neutrophil heterogeneity and crosstalk with cerebral-resident cells: therapeutic targets for ischemic stroke
AU - Yulin Yu
AU - Ying Bi
AU - Hao Song
AU - Dong Sun
AU - Siyu Huang
AU - Jianhua Wu
AU - Bin Mei
AU - Zhifang Li
PY - 2026
DA - 2026/08/11
JO - Journal of Translational Medicine
DO - 10.1186/s12967-026-08786-8
UR - https://doi.org/10.1186/s12967-026-08786-8
AB - Acute ischemic stroke elicits a robust inflammatory response within the brain. As one of the first peripheral immune cells to infiltrate the ischemic parenchyma, neutrophils show high heterogeneity and engage in complex crosstalk with resident brain cells. In this review, we first delineate the temporal dynamics of neutrophil mobilization after ischemic stroke, emphasizing their early and sustained accumulation in the ischemic brain. We then highlight recent advances in understanding neutrophil heterogeneity following ischemic stroke, with a particular focus on the skull–brain axis revealed by single-cell RNA sequencing. Additionally, we discuss the multifaceted interactions between neutrophils and parenchymal cells, including endothelial cells, neurons, microglia, and astrocytes after ischemic stroke. Finally, we expand the translational perspective by discussing emerging therapeutic approaches targeting neutrophils, NETosis, or specific neutrophil subsets in ischemic stroke. Unlike prior reviews that broadly focused on inflammatory networks, the present review specifically emphasizes the crosstalk between distinct neutrophil subsets and cerebral-resident cells, and integrates the latest single-cell RNA sequencing discoveries, including the newly identified skull–brain axis and a critical discussion of dichotomous models. Collectively, a comprehensive understanding of this intricate cellular network may help elucidate neutrophil heterogeneity, and future therapeutic strategies should shift from broad neutrophil depletion to precise targeting of pathogenic subsets to preserve potential repair functions.
SN - 1479-5876
ER -