Grant: Team Grant: Neuroinflammation

Many diseases of the central nervous system (CNS) show strong involvement of cells of the immune system, and are therefore considered inflammatory diseases of the CNS. Among these diseases are included multiple sclerosis (MS), Alzheimer's disease (AD) and even stroke, where immune cells invade the brain shortly after the cerebral infract. In this grant, we propose to investigate how cells of the immune system infiltrate the CNS. We will focus on a specific structure termed the blood brain barrier (BBB). The BBB is composed of endothelial cells that together with cells of the CNS form a structure that does not allow free movement of cells from the blood into the CNS. We will use state of the art microscopy to follow, in real time, how different immune cells of the blood enter the CNS. We will use new mouse strain that will allow us to manipulate important molecules expressed by cells of the BBB, to understand their role in promoting or preventing immune cells infiltration to the CNS. In addition, we will use our extensive collection of samples of human patients with CNS inflammatory diseases, to validate our findings in the human settings and to find new targets for the animal systems. Better understanding of the nature and the mechanisms that lead to the migration of immune cells into the CNS will allow us to better manipulate this process, and thus offer better future therapies for inflammatory diseases of the CNS.