Figure 2.

Myeloperoxidase (MPO)-related cascade after stroke.

Active microglia, monocytes, and neutrophils produce MPO when a stroke occurs. In addition to direct damage to the BBB, MPO can cause indirect damage. After a stroke occurs, myeloid immune cells, such as monocytes, neutrophils, and microglia, produce MPO, which participates in the reaction between H₂O₂ and Cl^–, generating HOCl and activating MMP7, MMP8, MMP9, and other MMPs, further damaging the BBB. MPO may also induce the production of 2-ClHA, which further damages the BBB. MPO can increase the activity of ROS, which can directly attack the BBB. ROS can also enhance the activity of MMP and reduce the activity of TIMP12. The simultaneous effects of these positive and negative regulatory actions can activate MMPs to a greater extent. MPO can promote the production of O₂^– and NO by iNOS and NADPH. In addition to increasing MMP activity, MPO can produce ONOO^–, and ONOO^– can further increase the activity of MMPs. This series of reactions will cause varying degrees of damage to the BBB, increasing the BBB permeability and aggravating secondary brain damage. 2-ClHA: 2-Chlorohexadecanoic acid; BBB: blood-brain barrier; Cl^–: chloride; H₂O₂: hydrogen peroxide; HOCl: oxidant chlorous acid; iNOS: inducible nitric oxide synthase; MG: microglia; NADPH: nicotinamide adenine dinucleotide phosphate; NO: nitric oxide; O₂^–: superoxide anion; ONOO^–: peroxynitrite ion; ROS: reactive oxygen species; TIMP12: tissue inhibitor of metalloproteinase 12; TJ: tight junction.