title: Dexamethasone prevents motor deficits and neurovascular damage produced by shiga toxin 2 and lipopolysaccharide in the mouse striatum.
abstract: Shiga toxin 2 (Stx2) from enterohemorrhagic Escherichia coli (EHEC) causes bloody diarrhea and Hemolytic Uremic Syndrome (HUS) that may derive to fatal neurological outcomes. Neurological abnormalities in the striatum are frequently observed in affected patients and in studies with animal models while motor disorders are usually associated with pyramidal and extra pyramidal systems. A translational murine model of encephalopathy was employed to demonstrate that systemic administration of a sublethal dose of Stx2 damaged the striatal microvasculature and astrocytes, increase the blood brain barrier permeability and caused neuronal degeneration. All these events were aggravated by lipopolysaccharide (LPS). The injury observed in the striatum coincided with locomotor behavioral alterations. The anti-inflammatory Dexamethasone resulted to prevent the observed neurologic and clinical signs, proving to be an effective drug. Therefore, the present work demonstrates that: (i) systemic sub-lethal Stx2 damages the striatal neurovascular unit as it succeeds to pass through the blood brain barrier. (ii) This damage is aggravated by the contribution of LPS which is also produced and secreted by EHEC, and (iii) the observed neurological alterations may be prevented by an anti-inflammatory treatment.
authors.affiliation: Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Instituto de Fisiología y Biofísica "Houssay" (IFIBIO), Facultad de Medicina, Universidad de Buenos Aires, Argentina.
authors.forename: Alipio
authors.initials: A
authors.lastname: Pinto
authors.affiliation: Centro Nacional de Control de Calidad de Biológicos (CNCCB), ANLIS "Dr. Carlos G. Malbrán", Buenos Aires, Argentina.
authors.forename: Adriana
authors.initials: A
authors.lastname: Cangelosi
authors.affiliation: Centro Nacional de Control de Calidad de Biológicos (CNCCB), ANLIS "Dr. Carlos G. Malbrán", Buenos Aires, Argentina.
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Geoghegan
authors.affiliation: Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Instituto de Fisiología y Biofísica "Houssay" (IFIBIO), Facultad de Medicina, Universidad de Buenos Aires, Argentina. Electronic address: jogol@fmed.uba.ar.
authors.forename: Jorge
authors.initials: J
authors.lastname: Goldstein
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001253:Astrocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology; D002561:Cerebrovascular Disorders / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology / Q000473:pathology; D003342:Corpus Striatum / Q000098:blood supply / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D003907:Dexamethasone / Q000494:pharmacology*; D004195:Disease Models, Animal; D004926:Escherichia coli; D005260:Female; D008070:Lipopolysaccharides / Q000633:toxicity*; D051379:Mice; D055806:Microvessels / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009069:Movement Disorders / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology; D022641:Shiga Toxin 2 / Q000633:toxicity*
chemical_list: D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D018696:Neuroprotective Agents; D022641:Shiga Toxin 2; D003907:Dexamethasone
keywords: Blood–Brain Barrier; Hemolytic Uremic Syndrome; encephalopathy; inflammation; microvasculature; neuronal damage