An Intrinsic Therapy Of Gold Nanoparticles In Focal Cerebral Ischemia-Reperfusion Injury In Rats

Background: Ischemia stroke is a leading cause of mortality and morbidityamong old people throughout the world, and the treatment options are limited.Therefore, a search for suitable regimens to rescue the central nervous system afterischemia has been a major research endeavor. Focal cerebral ischemia-reperfusion(I/R) injury is one of the most important pathological mechanisms during ischemiastroke. This process includes a series of cascades, such as inflammatory damage,apoptosis and oxidative stress, which constitute a complex regulatory network. Thus,efficient treatment should not only block the single target, but also play multipleprotective effects against I/R injury. Recent investigations are demonstratingpromising applications of gold nanoparticles (Au-NPs) to positively impact the healthcare system. The intrinsic therapies of Au-NPs including as anti-inflammatory andantirheumatic agents in the treatment of rheumatoid arthritis have elicited a lot ofinterest. However, little is known about the potential effect of Au-NPs on cerebral I/Rinjury.Objective: This study was designed to investigate the role of Au-NPs oncerebral I/R injury in the rat middle cerebral artery occlusion (MCAO) model.Methods: Adult male Sprague-Dawley rats were treated with Au-NPs (2mg/kg)randomly after90minutes of occlusion (beginning of reperfusion). Neurologic scoreswere evaluated at6h,12h,24h,48h and72h reperfusion, infarct volumes wereassessed after24h and72h reperfusion. Cytokines in serum were detected byCytometric Bead Array (CBA), meanwhile astrocytes and microglias activation werestudied by immunohistochemistry (IHC). TUNEL for cerebral apoptosis as well as Western Blotting for apoptosis-related molecules were performed in bothipsilateral-ischemic and contralateral-nonischemic hemispheres. Hepatorenal functionassay as well as histopathological analysis is tested.Results: Compared with vehicle group, the infarction volumes and neurologicdeficits significantly ameliorated in MCAO rats treated with20nm Au-NPs (p <0.05).These effects were not seen in5nm group. We found that20nm Au-NPs suppressedthe over activated astrocytes and microglias. The lever of IL-4and IL-10wasobviously elevated in serum after I/R by20nm, and TNF decreased in20nm treatedserum compared with Vehicle and5nm groups. Moreover, TUNEL staining showedthe greatly reduced number of apoptotic cells in the ischemic cortex in20nm Au-NPstreated brains. Western Blotting suggested that20nm Au-NPs limited the expressionof apoptosis relative molecules AIF, Cyt C and cleaved-caspase-3and facilitated theexpression of anti-apoptotic molecules such as Bcl-2and14-3-3ε in ipsilateral-ischemic brain. Loss of body weight and serum concentrations of urea, creatinine,ALT and AST were tested without significant augmentation，also liver and kidneywithout remarkable histological alterations in Vehicle or Au-NPs treated groups.Conclusion: Administration with20nm rather than5nm Au-NPs remarkablyameliorated the neurologic deficits and infarction volumes in MCAO rats without anysignificant toxicity. The mechanisms may involve anti-inflammation and anti-apoptosis.20nm Au-NPs may regulate immune system, reduce brain infarction andultimately induce functional recovery after I/R injury.