title: Decreased infarct size after focal cerebral ischemia in mice chronically infected with Toxoplasma gondii.
abstract: To determine whether Toxoplasma gondii infection could modify biological phenomena associated with brain ischemia, we investigated the effect of permanent middle cerebral artery occlusion (MCAO) on neuronal survival, inflammation and redox state in chronically infected mice. Infected animals showed a 40% to 50% decrease of infarct size compared with non-infected littermates 1, 4 and 14 days after MCAO. The resistance of infected mice may be associated with increased basal levels of anti-inflammatory cytokines and/or a marked reduction of the MCAO-related brain induction of two pro-inflammatory cytokines, tumor necrosis factor-alpha and interferon-gamma (IFNgamma). In addition, potential anti-inflammatory/neuroprotective factors such as nerve growth factor, suppressor of cytokine signaling-3, superoxide dismutase activity, uncoupling protein-2 and glutathione (GSH) were upregulated in the brain of infected mice. Consistent with a role of GSH in central cytokine regulation, GSH depletion by diethyl maleate inhibited Toxoplasma gondii lesion resistance by increasing the proinflammatory cytokine IFNgamma brain levels. Overall, these findings indicate that chronic toxoplasmosis decisively influences both the inflammatory molecular events and outcome of cerebral ischemia.
authors.affiliation: Department of Medicine, Division of Physiology, University of Fribourg, Chemin Du Musée 5, 1700 Fribourg, Switzerland. denis.arsenijevic@unifr.ch
authors.forename: D
authors.initials: D
authors.lastname: Arsenijevic
authors.forename: F
authors.initials: F
authors.lastname: de Bilbao
authors.forename: P
authors.initials: P
authors.lastname: Vallet
authors.forename: A
authors.initials: A
authors.lastname: Hemphill
authors.forename: B
authors.initials: B
authors.lastname: Gottstein
authors.forename: D
authors.initials: D
authors.lastname: Richard
authors.forename: P
authors.initials: P
authors.lastname: Giannakopoulos
authors.forename: W
authors.initials: W
authors.lastname: Langhans
mesh_terms: D000818:Animals; D001921:Brain / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D002545:Brain Ischemia / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D002908:Chronic Disease; D016207:Cytokines / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006963:Hyperphagia / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D020244:Infarction, Middle Cerebral Artery / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D007473:Ion Channels / Q000235:genetics; D008297:Male; D051379:Mice; D024101:Mitochondrial Proteins / Q000235:genetics; D009410:Nerve Degeneration / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics; D014122:Toxoplasma; D014123:Toxoplasmosis / Q000276:immunology* / Q000473:pathology*; D000071246:Uncoupling Protein 2; D015854:Up-Regulation
chemical_list: D016207:Cytokines; D007473:Ion Channels; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; C491411:Socs3 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; C000604390:Ucp2 protein, mouse; D000071246:Uncoupling Protein 2; D013482:Superoxide Dismutase; D005978:Glutathione