Reactive oxygen/nitrogen species (RONS) drive neuroinflammation in pneumococcal meningitis through three axes: pathogen-driven S. pneumoniae autolysis releases H2O2, which reacts with NO· to form peroxynitrite (ONOO-), inducing lipid peroxidation and mitochondrial DNA damage; enzymatic neutrophil myeloperoxidase (MPO) generates HOCl from H2O2/Cl-, activating MMP-9 to degrade collagen IV and disrupt BBB integrity; and metabolic IFN-γ-induced NOS2 sustains NO·, which reacts with O2- to form ONOO-, nitrating occludin/ZO-1 and destabilizing tight junctions. The gene discussed is MPO; the disease is pneumococcal meningitis.