The impact of systemic inflammation on the brain. (360G-Wellcome-207155_Z_17_Z)

Brain tissue from adult mice has already been collected, with a control group treated with saline and another treated with an attenuated strain of Salmonella typhimurium, triggering a systemic immune response including production of pro-inflammatory mediators that communicate with the brain triggering neuroinflammation and neuronal dysfunction. Selected groups of mice have been treated with two different inhibitors that block the activity of the cytokine IL-1beta, in order to investigate if this pro-inflammatory cytokine plays a direct role in neuroinflammation during systemic infection. In this project we will compare a small molecule with a biologic, both targeting cytokines, but via different mechanisms. The brain tissue will be examined using antibodies to stain activation markers of microglial cells (CD11b, FcRI, MHCII) and activation markers of cerebral endothelial cells (VCAM, ICAM, MHCII). Synaptic activation markers, from both the pre- and post-synaptic membranes, will be investigated by isolated mRNA from hippocampal enriched tissue. This investigation into phenotypic changes in microglial, cerebral endothelial cells and BBB function will be used to determine if the inhibition of IL-1beta is beneficial in reducing neuroinflammation as a result of systemic infection. This could later be applied to AD models, taking into consideration behavioural changes.