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Neuroprotective effects of ammonium tetrathiomolybdate, a slow-release sulfide donor, in a rodent model of regional stroke.
Mendonça, Bruna Pescador; Cardoso, Juliano Dos Santos; Michels, Monique; Vieira, Ana Carolina; Wendhausen, Diogo; Manfredini, Andressa; Singer, Mervyn; Dal-Pizzol, Felipe; Dyson, Alex.
Afiliación
  • Mendonça BP; Laboratory of Experimental Pathophysiology, University of Southern Santa Catarina, Criciúma, Brazil.
  • Cardoso JDS; Laboratory of Experimental Pathophysiology, University of Southern Santa Catarina, Criciúma, Brazil.
  • Michels M; Laboratory of Experimental Pathophysiology, University of Southern Santa Catarina, Criciúma, Brazil.
  • Vieira AC; Laboratory of Experimental Pathophysiology, University of Southern Santa Catarina, Criciúma, Brazil.
  • Wendhausen D; Laboratory of Experimental Pathophysiology, University of Southern Santa Catarina, Criciúma, Brazil.
  • Manfredini A; Laboratory of Experimental Pathophysiology, University of Southern Santa Catarina, Criciúma, Brazil.
  • Singer M; Bloomsbury Institute for Intensive Care Medicine, Division of Medicine, University College London, Gower St, London, WC1E 6BT, UK.
  • Dal-Pizzol F; Laboratory of Experimental Pathophysiology, University of Southern Santa Catarina, Criciúma, Brazil.
  • Dyson A; Laboratory of Experimental Pathophysiology, University of Southern Santa Catarina, Criciúma, Brazil. a.dyson@ucl.ac.uk.
Intensive Care Med Exp ; 8(1): 13, 2020 Apr 09.
Article en En | MEDLINE | ID: mdl-32274608
BACKGROUND: Several therapeutic strategies to rescue the brain from ischemic injury have improved outcomes after stroke; however, there is no treatment as yet for reperfusion injury, the secondary damage caused by necessary revascularization. Recently we characterized ammonium tetrathiomolybdate (ATTM), a drug used as a copper chelator over many decades in humans, as a new class of sulfide donor that shows efficacy in preclinical injury models. We hypothesized that ATTM could confer neuroprotection in a relevant rodent model of regional stroke. METHODS AND RESULTS: Brain ischemia was induced by transient (90-min) middle cerebral artery occlusion (tMCAO) in anesthetized Wistar rats. To mimic a clinical scenario, ATTM (or saline) was administered intravenously just prior to reperfusion. At 24 h or 7 days post-reperfusion, rats were assessed using functional (rotarod test, spontaneous locomotor activity), histological (infarct size), and molecular (anti-oxidant enzyme capacity, oxidative damage, and inflammation) outcome measurements. ATTM-treated animals showed improved functional activity at both 24 h and 7-days post-reperfusion, in parallel with a significant reduction in infarct size. These effects were additionally associated with increased brain antioxidant enzyme capacity, decreased oxidative damage, and a late (7-day) effect on pro-inflammatory cytokine levels and nitric oxide products. CONCLUSION: ATTM confers significant neuroprotection that, along with its known safety profile in humans, provides encouragement for its development as a novel adjunct therapy for revascularization following stroke.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Intensive Care Med Exp Año: 2020 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Alemania
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Intensive Care Med Exp Año: 2020 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Alemania