Therapeutic effect of gold nanoparticles in murine model of Ischemic stroke

• Grant number: 13/01013-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: April 01, 2013
• End date: December 31, 2013
• Field of knowledge: Biological Sciences - Pharmacology - Toxicology
• Principal Investigator: Stephen Fernandes de Paula Rodrigues
• Grantee: Kaléo Oliveira Bouéri Elache
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Fifteen million is the number of people affected by stroke per year worldwide, of which five million die (which is the second biggest killer disease in the world) and another five million become permanently disabled, which brings a huge burden on their families and the entire community. Stroke can be divided into ischemic or hemorrhagic. The ischemic stroke is 85%, while the hemorrhagic one is 15% of all cases. Treatment of acute ischemic stroke is accomplished with thrombolytic therapy using recombinant tissue plasminogen activator (rtPA), however, this agent must be administered within three hours of symptoms onset, which greatly limits its use since in most cases the time between recognition of symptoms and decision making for the administration of thrombolytic exceeds three hours. Knowing that the recruitment and activation of inflammatory cells in blood post-ischemic tissue may extend and accelerate tissue injury that is initiated by the ischemic insult, and that gold nanoparticles (AuNP) possess an anti-inflammatory effect, we decided to study the possible therapeutic effect of AuNP on the injury caused by acute focal cerebral ischemia followed by reperfusion tissue. To achieve this objective, male C57Bl6 mice will be divided into the following groups according to the treatments 30 minutes before and 5 hours after the onset of ischemia followed by cerebral reperfusion: 1) AuNP at a dose of 1x10*11 molecules/mouse, 2) distilled water (the AuNP vehicle), 3) saline solution (0.9%), 4) not treated and subjected to false surgery (sham) for cerebral ischemia. The treatments will be administered intravenously (iv) in a final volume of 100 µL. The occlusion of the middle cerebral artery is performed by the method of intraluminal filament after anesthesia with ketamine/xylazine. The monofilament is removed after twenty minutes of occlusion and experiments will be conducted after twenty-four hours of reperfusion. It will be assessed the effect of treatments on the integrity of the blood-brain barrier, by chromatographic assay after injection of Evans blue dye, the volume of cerebral infarction using the compound 2,3,5-triphenyl tetrazolium; and the expression of pro-and anti-inflammatory markers in the lesion focus, particularly IL-17, RANTES, and IL-10, by ELISA. Allied to the scientific importance of this project, it is worth mentioning the pioneering even in Brazil regarding to the animal model to be used, focal brain injury by I / R, which is being developed in the laboratory of Professor Ph.D Sandra HP Farsky, under the guidance of Ph.D Stephen Rodrigues, who has great experience in doing this model.(AU)