Research Progress of the Crosstalk between Neutrophil Extracellular Traps and Other Cells During CIRI Progression

Abstract

Ischemic stroke, also known as cerebral infarction, is a disease caused by cerebral vascular occlusion or arterial stenosis, leading to ischemia and hypoxia in brain tissue, which subsequently causes local brain tissue necrosis or softening. The main symptoms include sudden fainting, hemiplegia, facial deviation, sensory disturbances, and aphasia [1]. Ischemic stroke is characterized by high incidence, recurrence, disability, and mortality rates [2]. China has the highest incidence of ischemic stroke in the world, which is the leading cause of disease-related death in the country [3]. The pathological features of ischemic stroke mainly include neuroinflammation, thrombosis, neuronal injury, and disruption of the blood-brain barrier (BBB) integrity. Ischemia and hypoxia in brain tissue can disrupt the integrity of the BBB, increase vascular permeability, and allow peripheral immune cells (such as monocytes, B cells, and T cells) to infiltrate brain tissue, thereby further triggering neuroinflammatory responses and promoting thrombosis [4]. These pathological processes interact with each other and collectively exacerbate disease progression. Neutrophils are essential innate immune cells in the human immune system and the primary defense against infections [5]. Under normal physiological conditions, they patrol the bloodstream, ready to respond to infection signals. Once pathogens invade, neutrophils are rapidly activated and migrate to the site of infection, where they eliminate pathogens through phagocytosis and release antimicrobial peptides and enzymes to directly kill pathogens. In pathological conditions, the function of neutrophils changes, and over-activated neutrophils release large amounts of inflammatory mediators and proteases, leading to tissue damage and exacerbated inflammatory responses [6]. Neutrophil extracellular traps (NETs) are a unique web-like structure formed by activated neutrophils. Studies have shown that NETs can interact with microglia, endothelial cells, platelets, and neurons, thereby exacerbating pathological processes such as neuroinflammation, thrombosis, neuronal injury, and disruption of BBB integrity [7]. By studying the role of NETs in ischemic stroke, inhibiting the over-activation of neutrophils and the excessive formation of NETs to reduce post-stroke inflammatory responses and tissue damage has become a new therapeutic strategy for ischemic stroke, providing new treatment options and improving patient prognosis [8]. This article first explores the formation mechanisms of NETs, then summarizes the interactions between NETs and microglia, platelets, endothelial cells, and neurons in relation to ischemic stroke, and finally reviews the research progress on inhibiting NETs in ischemic stroke, providing new therapeutic targets for ischemic brain injury.