Neutrophil Dynamics in Ischemic Stroke

Neutrophils are the earliest immune cells recruited to the site of cerebral ischaemia, arriving within hours of arterial occlusion and persisting for days. Their migration across the compromised blood–brain barrier initiates a cascade of inflammatory events, including degranulation, release of neutrophil serine proteinases and formation of neutrophil extracellular traps. While these responses can exacerbate endothelial damage, blood–brain barrier breakdown and secondary tissue injury, neutrophils also exhibit phenotypic plasticity, adopting pro-inflammatory (N1) or reparative (N2) polarisation states that influence repair processes. Systemic factors such as metabolic comorbidities and intracellular regulators like specific kinases further modulate neutrophil activation and mobilisation. A balanced understanding of these dynamics is essential for the development of therapies that mitigate tissue damage without compromising host defence or reparative functions.

Research from Nature Portfolio

Recent foundational investigations have demonstrated that neutrophil-derived extracellular traps significantly impair post-ischaemic vascular repair. In experimental models, neutrophils accumulate in the peri-infarct cortex, with extracellular trap release peaking several days after stroke onset. Genetic or pharmacological inhibition of the enzyme responsible for trap formation reduced entrapment of chromatin in the vasculature, preserved blood–brain barrier integrity and enhanced neovascularisation. Interventions that disrupt existing traps via nucleases further improved microvascular remodelling and functional recovery, highlighting modulation of trap formation as a promising strategy in stroke rehabilitation.

Neutrophil Dynamics in Ischemic Stroke publication trend

The graph below shows the total number of articles in neutrophil dynamics in ischemic stroke across all publications each year (not limited to Nature Index journals).

Technical terms

Neutrophil extracellular traps (NETs): Web-like structures of DNA, histones and granule proteins expelled by activated neutrophils that can capture pathogens but also injure vascular endothelium.

Blood–brain barrier (BBB): A specialised endothelial interface that regulates the passage of cells and molecules into the brain; its disruption contributes to oedema and secondary injury in stroke.

Neutrophil serine proteinases (NSPs): A family of enzymes—including neutrophil elastase and proteinase 3—released during degranulation, which degrade extracellular matrix components and modulate inflammatory signalling.

Neutrophil polarisation: The process by which neutrophils adopt distinct functional states—pro-inflammatory (N1) or reparative (N2)—that differentially affect tissue damage and repair.

Hematopoietic progenitor kinase 1 (HPK1): An intracellular kinase that controls neutrophil activation pathways, influencing their migration, degranulation and inflammatory mediator release after ischaemic insult.

References

1. Association of admission neutrophil serine proteinases levels with the outcomes of acute ischemic stroke: a prospective cohort study. Journal of Neuroinflammation (2023).
2. Targeting HPK1 inhibits neutrophil responses to mitigate post-stroke lung and cerebral injuries. EMBO Molecular Medicine (2025).
3. Hypercholesterolemia triggers innate immune imbalance and transforms brain infarcts after ischemic stroke. Frontiers in Immunology (2025).
4. Neutrophil extracellular traps released by neutrophils impair revascularization and vascular remodeling after stroke. Nature Communications (2020).