title: How does the brain limit the severity of inflammation and tissue injury during bacterial meningitis?
abstract: The most devastating CNS bacterial infection, bacterial meningitis, has both acute and long-term neurologic consequences. The CNS defends itself against bacterial invasion through a combination of physical barriers (i.e. blood-brain barrier, meninges, and ependyma), which contain macrophages that express a range of pattern-recognition receptors that detect pathogens before they gain access to the CNS and cerebrospinal fluid. This activates an antipathogen response consisting of inflammatory cytokines, complement, and chemoattractants. Regulation of the antipathogen inflammatory response is essential for preventing irreversible brain injury and protecting stem cell populations in the ventricle wall. The severity of brain inflammation is regulated by the clearance of apoptotic inflammatory cells and neurons. Death signaling pathways are expressed by glia to stimulate apoptosis of neutrophils, lymphocytes, and damaged neurons and to regulate in flammation and remove necrotic cells. The emerging group of neuroimmunoregulatory molecules adjusts the balance of the anti-inflammatory and proinflammatory response to provide optimal conditions for effective clearance of pathogens and apoptotic cells but reduce the severity of the inflammatory response to prevent injury to brain cells, including stem cell populations. The neuroimmunoregulatory molecules and other CNS anti-inflammatory pathways represent potential therapeutic targets capable of reducing brain injury caused by bacterial infection.
authors.affiliation: Neuropathology Laboratory, Department of Cellular Pathology, Cardiff University Medical School, Cardiff, Wales, United Kingdom. jwneal@doctors.org.uk
authors.forename: James W
authors.initials: JW
authors.lastname: Neal
authors.forename: Philippe
authors.initials: P
authors.lastname: Gasque
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000473:pathology; D001921:Brain / Q000473:pathology*; D006801:Humans; D007249:Inflammation / Q000382:microbiology / Q000473:pathology; D016920:Meningitis, Bacterial / Q000473:pathology*; D012720:Severity of Illness Index