Thrombosis, Neuroinflammation, and Poststroke Infection: The Multifaceted Role of Neutrophils in Stroke

Figure 1

Neutrophil functions that can be targeted to reduce brain tissue destruction after stroke. Targets include factors involved in proinflammation, infiltration of immune cells, production of reactive oxygen species (ROS) and nitric oxide (NO), enzymatic functions of myeloperoxidase (MPO) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, and the release of neutrophil extracellular trap (NET) components. Inhibiting these pathways may also reduce thrombus formation and prevent recurrent stroke. In addition, after a stroke, patients undergo poststroke immune suppression, which includes impaired oxidative burst and NET formation, induced by catecholamines. Enhancing bacterial defense by targeting these mechanisms could decrease the risk of secondary infections. Therefore, poststroke immune modulation must take into account the fact that immune suppression has opposing effects in the central nervous system and in the periphery. HMGB-1: high mobility group protein box 1; VLA-4: very-late-antigen 4; CXCL-1: chemokine (C-X-C motif) ligand 1.