Neutrophil Extracellular Traps Exacerbate Ischemic Brain Damage.

Area of Science:

• Neuroscience
• Immunology
• Pathology

Background:

• Ischemic stroke triggers neuroinflammation, which can cause cell death and hinder repair.
• Neutrophils are key players in brain lesions post-stroke, exhibiting complex functions.
• Neutrophil extracellular traps (NETs), typically antimicrobial, are increasingly implicated in stroke pathology via NETosis.

Purpose of the Study:

• To review the formation, clearance, and spatiotemporal dynamics of neutrophils and NETs after ischemic damage.
• To elucidate the role of NETs in stroke-related phenomena, including blood-brain barrier disruption and thrombosis.
• To highlight the need for further investigation into NETs' effects on ischemic nerve cells, particularly in chronic phases.

Main Methods:

• Review of existing literature on neutrophil and NET behavior following ischemic stroke.
• Analysis of factors influencing NET formation, such as reactive oxygen species (ROS), PAD4 activation, and microenvironment.
• Examination of NET clearance mechanisms, including DNase 1 and microglial phagocytosis.

Main Results:

• NET formation depends on ROS and PAD4 activation, influenced by local pH, oxygen, and iron levels.
• Neutrophils and NETs appear in the perivascular space ipsilateral to infarcts 1-3 days post-stroke; parenchymal location is debated.
• NETs contribute to neurological deficit by damaging the blood-brain barrier and promoting thrombosis.

Conclusions:

• NETosis is a significant pathological process in ischemic stroke.
• NETs exert detrimental effects by compromising the blood-brain barrier and facilitating thrombosis.
• Further research is crucial to understand NETs' impact on neuronal function, especially in chronic stroke.