title: Pathologic mechanisms of influenza encephalitis with an abnormal expression of inflammatory cytokines and accumulation of mini-plasmin.
abstract: The pathogenesis of influenza encephalopathy or encephalitis is poorly understood. This review summarizes our recent studies of the roles played by inflammatory cytokines, inducible nitric oxide synthase (iNOS), adhesion molecules and mini-plasmin in influenza encephalitis. After the intranasal infection of newborn mice with the non-neurotropic strain of influenza A virus (IAV) Aichi/2/68/H3N2, encephalitis and severe brain edema were observed within 3-5 days. IAV-RNA and abnormalities in the blood-brain barrier permeability were detected in association with an increase in the mRNA expressions of endothelin-1, iNOS, and tumor necrosis factor-alpha. Furthermore, the accumulation in the brain capillaries of mini-plasmin, which proteolytically induces the viral envelope fusion activity and allows the virus to enter the cells, changes the brain from non-susceptible to susceptible to non-neurotropic IAV multiplication. The accumulation of mini-plasmin was markedly greater in newborn mice with an impaired mitochondrial fatty acid metabolism. These inflammatory mediators and the accumulation of mini-plasmin in the brain may play an important role in the onset and progression of LAV encephalitis.
authors.affiliation: Division of Enzyme Chemistry, Institute for Enzyme Research, The University of Tokushima, Tokushima, Japan.
authors.forename: Dengfu
authors.initials: D
authors.lastname: Yao
authors.forename: Masamichi
authors.initials: M
authors.lastname: Kuwajima
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kido
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000494:pharmacology; D001812:Blood-Brain Barrier; D001929:Brain Edema / Q000209:etiology; D016207:Cytokines / Q000502:physiology*; D018792:Encephalitis, Viral / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D016232:Endothelins / Q000502:physiology; D005227:Fatty Acids / Q000378:metabolism; D005341:Fibrinolysin / Q000502:physiology*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D009980:Influenza A virus / Q000472:pathogenicity; D007251:Influenza, Human / Q000150:complications*; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000187:drug effects; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D018384:Oxidative Stress; D010446:Peptide Fragments / Q000502:physiology*; D020033:Protein Isoforms / Q000502:physiology; D012202:Reye Syndrome / Q000209:etiology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics; D014774:Virulence
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D016232:Endothelins; D005227:Fatty Acids; D018836:Inflammation Mediators; D010446:Peptide Fragments; D020033:Protein Isoforms; D014409:Tumor Necrosis Factor-alpha; C019493:miniplasmin; D009569:Nitric Oxide; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D005341:Fibrinolysin