Inhibition of Neutrophil Extracellular Traps: A Potential Therapeutic Strategy for Hemorrhagic Stroke.

Abstract

Stroke is a major health problem with high mortality and morbidity rates, partly due to limited treatment options. Inflammation has a critical role in the secondary damage that occurs following a stroke event. Neutrophil extracellular traps (NETs) are released by neutrophils and contribute to the progression of neuroinflammation that further worsens brain damage. The prevention of NET formation at sites of brain damage has been reported to prevent neuroinflammation and improve neurological deficits. The aim of this article was to assess the importance of NETs as a treatment target for hemorrhagic stroke in light of the available evidence. NETs are network structures that consist of decondensed DNA strands coated with granule proteins such as citrullinated histones, neutrophile esterase (NE), myeloperoxidase (MPO), and high mobility group protein B1 (HMGB1). Peptidyl arginine deiminase type-IV (PAD4) plays a key role in the formation of NETs. Inhibitors of NET formation, such as the PAD4-specific inhibitor GSK484, are effective at preventing inflammation and thus ultimately reducing brain damage after stroke. In conclusion, inhibition of NETs offers a potential therapeutic strategy for hemorrhagic stroke, although further research is needed to clarify the role of NETs in this condition.