title: Pathophysiology of bacterial infection of the central nervous system and its putative role in the pathogenesis of behavioral changes.
abstract: Invasion of the central nervous system (CNS) by microorganisms is a severe and frequently fatal event during the course of many infectious diseases. It may lead to deafness, blindness, cerebral palsy, hydrocephalus, cognitive impairment or permanent neurological dysfunction in survivors. Pathogens can cross the blood-brain barrier by transcellular migration, paracellular migration and in infected macrophages. Pathogens may breach the blood-brain barrier and be recognized by antigen-presenting cells through the binding of Toll-like receptors. This induces the activation of nuclear factor kappa B or mitogen-activated protein kinase pathways and subsequently induces leukocyte infiltration and proliferation and the expression of numerous proteins involved in inflammation and the immune response. Many brain cells can produce cytokines, chemokines and other pro-inflammatory molecules in response to bacteria stimuli; as a consequence, polymorphonuclear cells are attracted and activated, and release large amounts of superoxide anion and nitric oxide, leading to peroxynitrite formation and oxidative stress. This cascade leads to lipid peroxidation, mitochondrial damage and blood-brain barrier breakdown, contributing to cellular injury during neuronal infection. Current evidence suggests that bacterial CNS infections can play a role in the etiopathogenesis of behavioral disorders by increasing pro-inflammatory cytokines and bacterial virulence factors. The aim of this review is to summarize the current knowledge of the relevant pathophysiologic steps in CNS infections.
authors.affiliation: Laboratory of Experimental Microbiology, Universidade do Extremo Sul Catarinense, Brazil. tba@unesc.net
authors.forename: Tatiana
authors.initials: T
authors.lastname: Barichello
authors.forename: Jaqueline S
authors.initials: JS
authors.lastname: Generoso
authors.forename: Graziele
authors.initials: G
authors.lastname: Milioli
authors.forename: Samuel G
authors.initials: SG
authors.lastname: Elias
authors.forename: Antônio Lúcio
authors.initials: AL
authors.lastname: Teixeira
mesh_terms: D001419:Bacteria / Q000472:pathogenicity; D016923:Cell Death; D002490:Central Nervous System / Q000276:immunology; D020806:Central Nervous System Bacterial Infections / Q000150:complications* / Q000503:physiopathology; D016207:Cytokines / Q000502:physiology; D006801:Humans; D007107:Immune System / Q000503:physiopathology; D007113:Immunity, Innate / Q000276:immunology; D001523:Mental Disorders / Q000209:etiology* / Q000503:physiopathology; D009474:Neurons
chemical_list: D016207:Cytokines