IFIBIO HOUSSAY   25014
INSTITUTO DE FISIOLOGIA Y BIOFISICA BERNARDO HOUSSAY
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Alteration of the neurovascular unit and the Inflammatory contribution during the encephalopathy produced by Shiga toxin 2 (STX2) from enterohemorrhagic Escherichia coli (EHEC) in the brain striatum of mice
Autor/es:
PINTO ALIPIO; BRENER GABRIELA; CANGELOSI ADRIANA; GEOGHEGAN PATRICIA; ARENAS DAVID; GOLDSTEIN JORGE
Lugar:
Boston, Massachusetts
Reunión:
Simposio; 9th Triennial International Symposium on Shiga Toxin (Verocytotoxin)-producing Escherichia coli (VTEC) meeting; 2015
Resumen:
Introduction: The striatum isinvolved in central motor pathways and is frequently affected in patientsinfected with EHEC. In addition to Stx2, LPS is secreted by the bacteria and may also contribute to the observedstriatal dysfunction. The aim of this study was to determine: i) whether LPSexacerbates the deleterious effect of Stx2 in the neurovascular unit (NU) ofthe striatum, and ii) the existence of a proinflammatory component thatcontributes to the clinical signs. Methods: NIH male mice wereinjected intravenously with Stx2+LPS or Stx2 or LPS or vehicle (control). Inaddition the same described groups were treated with Dexamethasone. Mice wereintracardially perfused with a fixative solution or with the addition of EvansBlue, to test the blood brain barrier (BBB) permeability. Their brains weresubjected to immunofluorescence with lectins to identify the microvasculature,anti-VEGF, anti-GFAP to identify astrocytes and anti-Stx2. Results and Discussion: Stx2+LPS maximallyincreased the permeability of the BBB (79+5 in arbitrary units [AU]),  increased the expression levels of GFAP (32+5 AU), and decreased completely theexpression levels of VEGF(63+5 positive particles) in comparison to controls. Immunopositivecells for Stx2 were higher in Stx2+LPS treated mice than Stx2 alone (80+6). Dexamethasone significantlyreduced the permeability of the BBB in Stx2+LPS treated mice and partiallyreverted the damage on the microvasculature and the changes observed in theexpression of VEGF, GFAP, and immunopositive Stx2 cells (P<0.05 byANOVA-Bonferroni post hoc test). We concluded that Stx2 alters theneurovascular unit of the striatum, LPS enhances the deleterious action of Stx2,and Dexamethasone determined the participation of pro-inflammatory mediatorstriggered by these toxins. Implications: The observedinflammatory component should be taken into account in order to establish newstudies and possibles therapies to treat this encephalopathy.