Neutrophil extracellular traps regulate ischemic stroke brain injury

Area of Science:

• Neuroscience
• Immunology
• Pathology

Background:

• Ischemic stroke triggers significant inflammation, worsening patient outcomes.
• Neutrophil extracellular traps (NETs) are implicated in inflammatory responses and stroke severity.

Purpose of the Study:

• To investigate the role of NET formation regulators in stroke.
• To explore the therapeutic potential of inhibiting NETs in ischemic stroke.

Main Methods:

• Examined NET-forming neutrophils in stroke patient brain tissue and plasma.
• Assessed plasma high-mobility group box 1 (HMGB1) and platelet surface expression.
• Investigated the effect of platelet depletion and HMGB1 knockout on NETs and stroke outcomes.
• Evaluated the efficacy of neonatal NET-inhibitory factor (nNIF) in preclinical stroke models.

Main Results:

• Elevated NET biomarkers correlated with worse stroke outcomes in patients.
• Platelets were identified as a key source of HMGB1 driving NET formation post-stroke.
• Reducing platelets or HMGB1 improved stroke outcomes by lowering NET levels.
• nNIF treatment reduced infarct size, improved neurological function, and enhanced survival in mice, even in aged and diabetic models.

Conclusions:

• NETs play a pathological role in ischemic stroke, exacerbated by platelet-derived HMGB1.
• nNIF demonstrates significant therapeutic potential for treating ischemic stroke, offering neuroprotection and functional recovery.