title: Pathophysiology of acute meningitis caused by Streptococcus pneumoniae and adjunctive therapy approaches.
abstract: Pneumococcal meningitis is a life-threatening disease characterized by an acute purulent infection affecting piamater, arachnoid and the subarachnoid space. The intense inflammatory host's response is potentially fatal and contributes to the neurological sequelae. Streptococcus pneumoniae colonizes the nasopharynx, followed by bacteremia, microbial invasion and blood-brain barrier traversal. S. pneumoniae is recognized by antigen-presenting cells through the binding of Toll-like receptors inducing the activation of factor nuclear kappa B or mitogen-activated protein kinase pathways and subsequent up-regulation of lymphocyte populations and expression of numerous proteins involved in inflammation and immune response. Many brain cells can produce cytokines, chemokines and others pro-inflammatory molecules in response to bacteria stimuli, as consequence, polymorphonuclear are attracted, activated and released in large amounts of superoxide anion and nitric oxide, leading to the peroxynitrite formation, generating oxidative stress. This cascade leads to lipid peroxidation, mitochondrial damage, blood-brain barrier breakdown contributing to cell injury during pneumococcal meningitis.
authors.affiliation: Laboratório de Microbiologia Experimental, Instituto Nacional de Ciência e Tecnologia Translacional em Medicina, Universidade do Extremo Sul Catarinense, Criciúma, SC, 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: Allan
authors.initials: A
authors.lastname: Collodel
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Moreira
authors.forename: Sérgio Monteiro de
authors.initials: SM
authors.lastname: Almeida
mesh_terms: D000208:Acute Disease; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008586:Meningitis, Pneumococcal / Q000188:drug therapy / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology; D009666:Nose / Q000382:microbiology; D018384:Oxidative Stress / Q000502:physiology; D013296:Streptococcus pneumoniae
chemical_list: D000305:Adrenal Cortex Hormones; D016207:Cytokines; D020782:Matrix Metalloproteinases