University of Kentucky, USA
Scientific Tracks Abstracts: Neurochem Neuropharm
Many studies have recently demonstrated that the spleen plays a central role in the immune response to stroke, yet few have been successful in describing the precise splenic mechanisms leading to neurodegeneration. Our laboratory was the first to demonstrate that splenectomy decreases infarct volume. Importantly, we have spent the past decade elucidating the inflammatory signals and cell types involved. We have identified the splenic immune cells (monocytes, NK and T) that migrate to the injured hemisphere following experimental stroke. We have also shown that systemic administration of the proinflammatory cytokine IFN√?¬≥ abolished the protective effects of splenectomy, and administration of IFN√?¬≥ blocking antibodies reduced injury. Moreover, IFN√?¬≥ activates and induces expression of IP-10 in microglia. IP-10 attracts IFN√?¬≥-expressing T cells to the injured hemisphere and drives a Th1 response while inhibiting the Th2 one. The spleen-derived neurodestructive signaling involves IFN√?¬≥-associated activation of microglia, which leads to a feed forward signal through IP10 to attract more IFN√?¬≥. This leads to the additional expression of IP-10 in M1 microglia to further exacerbate stroke-induced neurodegeneration. This splenic response provides a therapeutic target for novels treatments to reduce stroke-induced neurodegeneration.
Keith Pennypacker has completed his PhD from Penn State University and Post-doctoral studies from National Institute of Environmental Sciences. He is a Professor in the Department of Molecular Pharmacology and Physiology. He has published more than 100 papers in peer-reviewed journals and has been serving as an Editorial Board Member of Translational Stroke Research and Toxicology and Applied Pharmacology.