Oxidative stress in bacterial meningitis.
Fifty years after the advent of antibiotics for clinical use, the rates of morbidity and mortality associated with bacterial meningitis remain high. The unfavourable clinical outcome is often due to intracranial complications including cerebrovascular insults, raised intracranial pressure, hydrocephalus, and brain edema. Reactive oxygen species (ROS) are known effector molecules in the antimicrobial armature of polymorphonuclear and mononuclear phagocytes. However, over the last decade, there has been a substantial body of work implicating a central role of ROS in the development of intracranial complications and brain damage in bacterial meningitis. Recently, it also became evident that reactive nitrogen species (RNS), especially nitric oxide, are important mediators of meningitis-associated pathophysiological changes, at least during the early phase of the disease. There is now substantial evidence that much of the oxidative injury associated by simultaneous production of superoxide and nitric oxide is mediated by the strong oxidant peroxynitrite. ROS and peroxynitrite can be cytotoxic via a number of independent mechanisms. Their cytotoxic effects include initiation of lipid peroxidation and induction of DNA single strand breakage. Damaged DNA activates poly(ADP-ribose) polymerase (PARP). Recent experimental data propose a role of lipid peroxidation and PARP activation in the development of meningitis-associated intracranial complications and brain injury. Agents which interfere with the production of ROS and peroxynitrite, as well as with PARP activation and lipid peroxidation may represent novel, therapeutic strategies to limit meningitis-associated brain damage, and, thus, to improve the outcome of this serious disease.
Koedel
U
U
Department of Neurology, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Germany.
Pfister
H W
HW
D000818:Animals; D001930:Brain Injuries / Q000378:metabolism; D006790:Host-Parasite Interactions; D006801:Humans; D015227:Lipid Peroxidation / Q000502:physiology; D016920:Meningitis, Bacterial / Q000378:metabolism* / Q000473:pathology; D009566:Nitrates / Q000378:metabolism / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology; D016877:Oxidants / Q000378:metabolism / Q000502:physiology; D018384:Oxidative Stress; D011065:Poly(ADP-ribose) Polymerases / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism / Q000502:physiology*